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1,292 results on '"Hacohen, Nir"'

1. Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis

Author

Baillie, J. Kenneth, Angus, Derek, Burnham, Katie, Calandra, Thierry, Calfee, Carolyn, Gutteridge, Alex, Hacohen, Nir, Khatri, Purvesh, Langley, Raymond, Ma’ayan, Avi, Marshall, John, Maslove, David, Prescott, Hallie C., Rowan, Kathy, Scicluna, Brendon P., Seymour, Christopher, Shankar-Hari, Manu, Shapiro, Nathan, Joost Wiersinga, W., Singer, Mervyn, and Randolph, Adrienne G.

Published
2024
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3. Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis.

Author

Fava, Andrea, Buyon, Jill, Magder, Laurence, Hodgin, Jeff, Rosenberg, Avi, Demeke, Dawit, Rao, Deepak, Arazi, Arnon, Celia, Alessandra, Putterman, Chaim, Anolik, Jennifer, Barnas, Jennifer, DallEra, Maria, Wofsy, David, Furie, Richard, Kamen, Diane, Kalunian, Kenneth, James, Judith, Guthridge, Joel, Atta, Mohamed, Monroy Trujillo, Jose, Fine, Derek, Clancy, Robert, Belmont, H, Izmirly, Peter, Apruzzese, William, Goldman, Daniel, Berthier, Celine, Hoover, Paul, Hacohen, Nir, Raychaudhuri, Soumya, Davidson, Anne, Diamond, Betty, and Petri, Michelle

Subjects
Autoimmunity, Diagnostics, Lupus, Nephrology, Proteomics, Humans, Lupus Nephritis, Proteomics, Proteinuria, Inflammation, Aggression
Abstract

Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

Published
2024

4. The commitment of the human cell atlas to humanity

Author

Amit, Ido, Ardlie, Kristin, Arzuaga, Fabiana, Awandare, Gordon, Bader, Gary, Bernier, Alexander, Carninci, Piero, Donnelly, Stacey, Eils, Roland, Forrest, Alistair R. R., Greely, Henry T., Guigo, Roderic, Hacohen, Nir, Haniffa, Muzlifah, Kirby, Emily Sarah, Knoppers, Bartha Maria, Kriegstein, Arnold, Lein, Ed S., Linnarsson, Sten, Majumder, Partha P., Merad, Miriam, Meyer, Kerstin, Mhlanga, Musa M., Nolan, Garry, Ntusi, Ntobeko A. B., Pe’er, Dana, Prabhakar, Shyam, Raven-Adams, Maili, Regev, Aviv, Rozenblatt-Rosen, Orit, Saha, Senjuti, Saltzman, Andrea, Shalek, Alex K., Shin, Jay W., Stunnenberg, Henk, Teichmann, Sarah A., Tickle, Timothy, Villani, Alexandra-Chloe, Wells, Christine, Wold, Barbara, Yang, Huanming, and Zhuang, Xiaowei

Published
2024
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5. Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial

Author

Mooradian, Meghan J., Fintelmann, Florian J., LaSalle, Thomas J., Simon, Judit, Graur, Alexander, Muzikansky, Alona, Mino-Kenudson, Mari, Shalhout, Sophia, Kaufman, Howard L., Jenkins, Russell W., Lawrence, Donald, Lawless, Aleigha, Sharova, Tatyana, Uppot, Raul N., Fang, Jacy, Blaum, Emily M., Gonye, Anna L. K., Gushterova, Irena, Boland, Genevieve M., Azzoli, Christopher, Hacohen, Nir, Sade-Feldman, Moshe, and Sullivan, Ryan J.

Published
2024
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6. Single-cell transcriptomic analyses reveal distinct immune cell contributions to epithelial barrier dysfunction in checkpoint inhibitor colitis

Author

Thomas, Molly Fisher, Slowikowski, Kamil, Manakongtreecheep, Kasidet, Sen, Pritha, Samanta, Nandini, Tantivit, Jessica, Nasrallah, Mazen, Zubiri, Leyre, Smith, Neal P., Tirard, Alice, Ramesh, Swetha, Arnold, Benjamin Y., Nieman, Linda T., Chen, Jonathan H., Eisenhaure, Thomas, Pelka, Karin, Song, Yuhui, Xu, Katherine H., Jorgji, Vjola, Pinto, Christopher J., Sharova, Tatyana, Glasser, Rachel, Chan, PuiYee, Sullivan, Ryan J., Khalili, Hamed, Juric, Dejan, Boland, Genevieve M., Dougan, Michael, Hacohen, Nir, Li, Bo, Reynolds, Kerry L., and Villani, Alexandra-Chloé

Published
2024
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7. High-throughput RNA isoform sequencing using programmed cDNA concatenation

Author

Al’Khafaji, Aziz M., Smith, Jonathan T., Garimella, Kiran V., Babadi, Mehrtash, Popic, Victoria, Sade-Feldman, Moshe, Gatzen, Michael, Sarkizova, Siranush, Schwartz, Marc A., Blaum, Emily M., Day, Allyson, Costello, Maura, Bowers, Tera, Gabriel, Stacey, Banks, Eric, Philippakis, Anthony A., Boland, Genevieve M., Blainey, Paul C., and Hacohen, Nir

Published
2024
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8. Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy

Author

Chen, Jonathan H., Nieman, Linda T., Spurrell, Maxwell, Jorgji, Vjola, Elmelech, Liad, Richieri, Peter, Xu, Katherine H., Madhu, Roopa, Parikh, Milan, Zamora, Izabella, Mehta, Arnav, Nabel, Christopher S., Freeman, Samuel S., Pirl, Joshua D., Lu, Chenyue, Meador, Catherine B., Barth, Jaimie L., Sakhi, Mustafa, Tang, Alexander L., Sarkizova, Siranush, Price, Colles, Fernandez, Nicolas F., Emanuel, George, He, Jiang, Van Raay, Katrina, Reeves, Jason W., Yizhak, Keren, Hofree, Matan, Shih, Angela, Sade-Feldman, Moshe, Boland, Genevieve M., Pelka, Karin, Aryee, Martin J., Mino-Kenudson, Mari, Gainor, Justin F., Korsunsky, Ilya, and Hacohen, Nir

Published
2024
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9. Exposure of iPSC-derived human microglia to brain substrates enables the generation and manipulation of diverse transcriptional states in vitro

Author

Dolan, Michael-John, Therrien, Martine, Jereb, Saša, Kamath, Tushar, Gazestani, Vahid, Atkeson, Trevor, Marsh, Samuel E, Goeva, Aleksandrina, Lojek, Neal M, Murphy, Sarah, White, Cassandra M, Joung, Julia, Liu, Bingxu, Limone, Francesco, Eggan, Kevin, Hacohen, Nir, Bernstein, Bradley E, Glass, Christopher K, Leinonen, Ville, Blurton-Jones, Mathew, Zhang, Feng, Epstein, Charles B, Macosko, Evan Z, and Stevens, Beth

Subjects
Biochemistry and Cell Biology, Biological Sciences, Brain Disorders, Stem Cell Research, Human Genome, Genetics, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Alzheimer's Disease, Dementia, Acquired Cognitive Impairment, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Generic health relevance, Humans, Microglia, Induced Pluripotent Stem Cells, Alzheimer Disease, Brain, Neurodegenerative Diseases, Immunology, Biochemistry and cell biology
Abstract

Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer's disease. These cells adopt distinct transcriptional subtypes known as states. Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells. Here, we developed a platform for modeling human microglia transcriptional states in vitro. We found that exposure of human stem-cell-differentiated microglia to synaptosomes, myelin debris, apoptotic neurons or synthetic amyloid-beta fibrils generated transcriptional diversity that mapped to gene signatures identified in human brain microglia, including disease-associated microglia, a state enriched in neurodegenerative diseases. Using a new lentiviral approach, we demonstrated that the transcription factor MITF drives a disease-associated transcriptional signature and a highly phagocytic state. Together, these tools enable the manipulation and functional interrogation of human microglial states in both homeostatic and disease-relevant contexts.

Published
2023

10. Unsupervised Protein-Ligand Binding Energy Prediction via Neural Euler's Rotation Equation

Author

Jin, Wengong, Sarkizova, Siranush, Chen, Xun, Hacohen, Nir, and Uhler, Caroline

Subjects
Quantitative Biology - Biomolecules, Computer Science - Machine Learning
Abstract

Protein-ligand binding prediction is a fundamental problem in AI-driven drug discovery. Prior work focused on supervised learning methods using a large set of binding affinity data for small molecules, but it is hard to apply the same strategy to other drug classes like antibodies as labelled data is limited. In this paper, we explore unsupervised approaches and reformulate binding energy prediction as a generative modeling task. Specifically, we train an energy-based model on a set of unlabelled protein-ligand complexes using SE(3) denoising score matching and interpret its log-likelihood as binding affinity. Our key contribution is a new equivariant rotation prediction network called Neural Euler's Rotation Equations (NERE) for SE(3) score matching. It predicts a rotation by modeling the force and torque between protein and ligand atoms, where the force is defined as the gradient of an energy function with respect to atom coordinates. We evaluate NERE on protein-ligand and antibody-antigen binding affinity prediction benchmarks. Our model outperforms all unsupervised baselines (physics-based and statistical potentials) and matches supervised learning methods in the antibody case.

Published
2023

14. Urine Proteomics and Renal Single‐Cell Transcriptomics Implicate Interleukin‐16 in Lupus Nephritis

Author

Fava, Andrea, Rao, Deepak A, Mohan, Chandra, Zhang, Ting, Rosenberg, Avi, Fenaroli, Paride, Belmont, H Michael, Izmirly, Peter, Clancy, Robert, Trujillo, Jose Monroy, Fine, Derek, Arazi, Arnon, Berthier, Celine C, Davidson, Anne, James, Judith A, Diamond, Betty, Hacohen, Nir, Wofsy, David, Raychaudhuri, Soumya, Apruzzese, William, Network, the Accelerating Medicines Partnership in Rheumatoid Arthritis and Systemic Lupus Erythematosus, Buyon, Jill, and Petri, Michelle

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Clinical Research, Lupus, Autoimmune Disease, Biotechnology, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Renal and urogenital, Inflammatory and immune system, Biological Products, Biomarkers, Female, Humans, Interleukin-16, Kidney, Lupus Nephritis, Male, Proteomics, Single-Cell Analysis, Transcriptome, Accelerating Medicines Partnership in Rheumatoid Arthritis and Systemic Lupus Erythematosus Network, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveCurrent lupus nephritis (LN) treatments are effective in only 30% of patients, emphasizing the need for novel therapeutic strategies. We undertook this study to develop mechanistic hypotheses and explore novel biomarkers by analyzing the longitudinal urinary proteomic profiles in LN patients undergoing treatment.MethodsWe quantified 1,000 urinary proteins in 30 patients with LN at the time of the diagnostic renal biopsy and after 3, 6, and 12 months. The proteins and molecular pathways detected in the urine proteome were then analyzed with respect to baseline clinical features and longitudinal trajectories. The intrarenal expression of candidate biomarkers was evaluated using single-cell transcriptomics of renal biopsy sections from LN patients.ResultsOur analysis revealed multiple biologic pathways, including chemotaxis, neutrophil activation, platelet degranulation, and extracellular matrix organization, which could be noninvasively quantified and monitored in the urine. We identified 237 urinary biomarkers associated with LN, as compared to controls without systemic lupus erythematosus. Interleukin-16 (IL-16), CD163, and transforming growth factor β mirrored intrarenal nephritis activity. Response to treatment was paralleled by a reduction in urinary IL-16, a CD4 ligand with proinflammatory and chemotactic properties. Single-cell RNA sequencing independently demonstrated that IL16 is the second most expressed cytokine by most infiltrating immune cells in LN kidneys. IL-16-producing cells were found at key sites of kidney injury.ConclusionUrine proteomics may profoundly change the diagnosis and management of LN by noninvasively monitoring active intrarenal biologic pathways. These findings implicate IL-16 in LN pathogenesis, designating it as a potentially treatable target and biomarker.

Published
2022

15. Precision Medicine in Nephrology: An Integrative Framework of Multidimensional Data in the Kidney Precision Medicine Project

Author

Lake, Blue, Zhang, Kun, Lecker, Stewart, Morales, Alexander, Bogen, Steve, Amodu, Afolarin A., Beck, Laurence, Henderson, Joel, Ilori, Titlayo, Maikhor, Shana, Onul, Ingrid, Schmidt, Insa, Verma, Ashish, Waikar, Sushrut, Yadati, Pranav, Yu, Guanghao, Colona, Mia R., McMahon, Gearoid, Hacohen, Nir, Greka, Anna, Hoover, Paul J., Marshall, Jamie L., Aulisio, Mark, Bush, William, Chen, Yijiang, Crawford, Dana, Madabhushi, Anant, Viswanathan, Vidya S., Bush, Lakeshia, Cooperman, Leslie, Gadegbeku, Crystal, Herlitz, Leal, Jolly, Stacey, Nguyen, Jane, O’Malley, Charles, O’Toole, John, Palmer, Ellen, Poggio, Emilio, Spates-Harden, Kassandra, Sedor, John, Sendrey, Dianna, Taliercio, Jonathan, Appelbaum, Paul, Balderes, Olivia, Barasch, Jonathan, Berroue, Cecilia, Bomback, Andrew, Canetta, Pietro A., D’Agati, Vivette, Kiryluk, Krzysztof, Kudose, Satoru, Mehl, Karla, Sabatello, Maya, Shang, Ning, de Pinho Gonçalves, Joana, Lardenoije, Roy, Migas, Lukasz, Van de Plas, Raf, Rennke, Helmut, Azeloglu, Evren, Campbell, Kirk, Coca, Steven, He, Cijang, He, John, Iyengar, Srinivas Ravi, Lefferts, Seanee, Nadkarni, Girish, Patel, Marissa, Tokita, Joji, Ward, Stephen, Xiong, Yuguang, Verdoes, Abraham, Sabo, Angela, Barwinska, Daria, Gisch, Debora Lidia, Williams, James, Kelly, Katherine, Dunn, Kenneth, Asghari, Mahla, Eadon, Michael, Ferkowicz, Michael, Dagher, Pierre, Ferreira, Ricardo Melo, Winfree, Seth, Bledsoe, Sharon, Wofford, Stephanie, El-Achkar, Tarek, Sutton, Timothy, Bowen, William, Cheng, Ying-Hua, Slade, Austen, Record, Elizabeth, Cheng, Yinghua, Borner, Katy, Herr, Bruce, Jain, Yashvardhan, Quardokus, Ellen, Atta, Mohamed, Bernard, Lauren, Menez, Steven, Parikh, Chirag, Corona Villalobos, Celia Pamela, Wang, Ashley, Wen, Yumeng, Xu, Alan, Chen, Sarah, Donohoe, Isabel, Johansen, Camille, Rosas, Sylvia, Sun, Jennifer, Ardayfio, Joseph, Bebiak, Jack, Campbell, Taneisha, Fox, Monica, Knight, Richard, Koewler, Robert, Pinkeney, Roy, Saul, John, Shpigel, Anna, Prasad, Pottumarthi, Madhavan, Sethu M., Parikh, Samir, Rovin, Brad, Shapiro, John P., Anderton, Christopher, Lukowski, Jessica, Pasa-Tolic, Ljiljana, Velickovic, Dusan, Oliver, George, Mao, Weiguang, Sealfon, Rachel, Troyanskaya, Olga, Pollack, Ari, Goltsev, Yury, Ginley, Brandon, Anjani, Kavya, Laszik, Zoltan G., Mukatash, Tariq, Nolan, Garry, Beyda, David, Bracamonte, Erika, Brosius, Frank, Campos, Baltazar, Marquez, Nicole, Mendoza, Katherine, Scott, Raymond, Thajudeen, Bijin, Tsosie, Rebecca, Woodhead, Gregory, Saunders, Milda, Alloway, Rita R., Lee, Paul J., Rike, Adele, Shi, Tiffany, Woodle, E. Steve, Bjornstad, Petter, Hsieh, Elena, Kendrick, Jessica, Pyle, Laura, Thurman, Joshua, Vinovskis, Carissa, Wrobel, Julia, Lucarelli, Nicholas, Sarder, Pinaki, Bui, James, Carmona-Powell; Ron Gaba, Eunice, Kelly, Tanika, Lash, James, Meza, Natalie, Redmond, Devona, Renteria, Amada, Ricardo, Ana, Setty, Suman, Srivastava, Anand, Alakwaa, Fadhl, Ascani, Heather, Balis, Ul, Bitzer, Markus, Blanc, Victoria, Bonevich, Nikki, Conser, Ninive, Demeke, Dawit, Dull, Rachel, Eddy, Sean, Frey, Renee, Hartman, John, He, Yongqun Oliver, Hodgin, Jeffrey, Kretzler, Matthias, Lienczewski, Chrysta, Luo, Jinghui, Mariani, Laura, McCown, Phillip, Menon, Rajasree, Nair, Viji, Otto, Edgar, Reamy, Rebecca, Rose, Michael, Schaub, Jennifer, Steck, Becky, Wright, Zachary, Coleman, Alyson, Henderson-Brown; Jerica Berge, Dorisann, Caramori, Maria Luiza, Adeyi, Oyedele, Nachman, Patrick, Safadi, Sami, Flanagan, Siobhan, Ma, Sisi, Klett, Susan, Wolf, Susan, Harindhanavudhi, Tasma, Rao, Via, Bream, Peter, Froment, Anne, Kelley, Sara, Mottl, Amy, Chaudhury; Evan Zeitler, Prabir Roy, Bender, Filitsa, Elder, Michele, Gilliam, Matthew, Hall, Daniel E., Kellum, John A., Murugan, Raghavan, Palevsky, Paul, Rosengart, Matthew, Tan, Roderick, Tublin, Mitchell, Winters, James, Bansal, Shweta, Montellano, Richard, Pamreddy, Annapurna, Sharma, Kumar, Venkatachalam, Manjeri, Ye, Hongping, Zhang, Guanshi, Basit, Mujeeb, Cai, Qi, Hendricks, Allen, Hedayati, Susan, Kermani, Asra, Lee, Simon C., Ma, Shihong, Miller, Richard Tyler, Moe, Orson W., Park, Harold, Patel, Jiten, Pillai, Anil, Sambandam, Kamalanathan, Torrealba, Jose, Toto, Robert D., Vazquez, Miguel, Wang, Nancy, Wen, Natasha, Zhang, Dianbo, Alpers, Charles, Berglund, Ashley, Berry, Brooke, Blank, Kristina, Brown, Keith, Carson, Jonas, Daniel, Stephen, de Boer, Ian H., Dighe, Ashveena L., Dowd, Frederick, Grewenow, Stephanie M., Himmelfarb, Jonathan, Hoofnagle, Andrew, Jefferson, Nichole, Larson, Brandon, Limonte, Christine, McClelland, Robyn, Mooney, Sean, Nam, Yunbi, Park, Christopher, Phuong, Jimmy, Rezaei, Kasra, Roberts, Glenda, Sarkisova, Natalya, Shankland, Stuart, Snyder, Jaime, Stutzke, Christy, Tuttle, Katherine, Wangperawong, Artit, Wilcox, Adam, Williams, Kayleen, Young, Bessie, Allen, Jamie, Caprioli, Richard M., de Caestecker, Mark, Djambazova, Katerina, Dufresne, Martin, Farrow, Melissa, Fogo, Agnes, Sharman, Kavya, Spraggins, Jeffrey, Basta, Jeannine, Conlon, Kristine, Diettman, Sabine M., Gaut, Joseph, Kaushal, Madhurima, Jain, Sanjay, Knoten, Amanda, Minor, Brittany, Nwanne, Gerald, Vijayan, Anitha, Zhang, Bo, Arora, Tanima, Cantley, Lloyd, Victoria Castro, Angela M., Kakade, Vijayakumar, Moeckel, Gilbert, Moledina, Dennis, Shaw, Melissa, Wilson, Francis P., El-Achkar, Tarek M., and Eadon, Michael T.

Published
2024
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16. Spatially organized multicellular immune hubs in human colorectal cancer.

Author

Pelka, Karin, Hofree, Matan, Chen, Jonathan, Sarkizova, Siranush, Pirl, Joshua, Jorgji, Vjola, Bejnood, Alborz, Dionne, Danielle, Ge, William, Xu, Katherine, Chao, Sherry, Zollinger, Daniel, Lieb, David, Reeves, Jason, Fuhrman, Christopher, Hoang, Margaret, Delorey, Toni, Nguyen, Lan, Waldman, Julia, Klapholz, Max, Wakiro, Isaac, Cohen, Ofir, Albers, Julian, Smillie, Christopher, Cuoco, Michael, Wu, Jingyi, Su, Mei-Ju, Yeung, Jason, Vijaykumar, Brinda, Magnuson, Angela, Asinovski, Natasha, Moll, Tabea, Goder-Reiser, Max, Applebaum, Anise, Brais, Lauren, DelloStritto, Laura, Denning, Sarah, Phillips, Susannah, Hill, Emma, Meehan, Julia, Frederick, Dennie, Sharova, Tatyana, Kanodia, Abhay, Todres, Ellen, Jané-Valbuena, Judit, Biton, Moshe, Izar, Benjamin, Lambden, Conner, Clancy, Thomas, Bleday, Ronald, Melnitchouk, Nelya, Irani, Jennifer, Kunitake, Hiroko, Berger, David, Srivastava, Amitabh, Hornick, Jason, Ogino, Shuji, Rotem, Asaf, Vigneau, Sébastien, Johnson, Bruce, Corcoran, Ryan, Sharpe, Arlene, Kuchroo, Vijay, Ng, Kimmie, Giannakis, Marios, Nieman, Linda, Boland, Genevieve, Aguirre, Andrew, Anderson, Ana, Rozenblatt-Rosen, Orit, Regev, Aviv, and Hacohen, Nir

Subjects
MSI, MSS, anti-tumor immunity, cell-cell interactions, colorectal cancer, mismatch repair-deficient, mismatch repair-proficient, scRNA-seq, spatial, tumor atlas, Bone Morphogenetic Proteins, Cancer-Associated Fibroblasts, Cell Compartmentation, Cell Line, Tumor, Chemokines, Cohort Studies, Colorectal Neoplasms, DNA Mismatch Repair, Endothelial Cells, Gene Expression Regulation, Neoplastic, Humans, Immunity, Inflammation, Monocytes, Myeloid Cells, Neutrophils, Stromal Cells, T-Lymphocytes, Transcription, Genetic
Abstract

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across tumors from affected individuals and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T cell-attracting chemokines. By identifying interacting cellular programs, we reveal the logic underlying spatially organized immune-malignant cell networks.

Published
2021

17. Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitis

Author

Cui, Ang, Li, Bo, Wallace, Michael S., Gonye, Anna L.K., Oetheimer, Christopher, Patel, Hailey, Tonnerre, Pierre, Holmes, Jacinta A., Lieb, David, Yao, Brianna S., Ma, Aileen, Roberts, Kela, Damasio, Marcos, Chen, Jonathan H., Piou, Daphnee, Carlton-Smith, Charles, Brown, Joelle, Mylvaganam, Ravi, Hon Fung, Jeremy Man, Sade-Feldman, Moshe, Aneja, Jasneet, Gustafson, Jenna, Epstein, Eliana T., Salloum, Shadi, Brisac, Cynthia, Thabet, Ashraf, Kim, Arthur Y., Lauer, Georg M., Hacohen, Nir, Chung, Raymond T., and Alatrakchi, Nadia

Published
2024
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18. The HLA-II immunopeptidome of SARS-CoV-2

Author

Weingarten-Gabbay, Shira, Chen, Da-Yuan, Sarkizova, Siranush, Taylor, Hannah B., Gentili, Matteo, Hernandez, Gabrielle M., Pearlman, Leah R., Bauer, Matthew R., Rice, Charles M., Clauser, Karl R., Hacohen, Nir, Carr, Steven A., Abelin, Jennifer G., Saeed, Mohsan, and Sabeti, Pardis C.

Published
2024
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19. Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer

Author

Ravi, Arvind, Hellmann, Matthew D., Arniella, Monica B., Holton, Mark, Freeman, Samuel S., Naranbhai, Vivek, Stewart, Chip, Leshchiner, Ignaty, Kim, Jaegil, Akiyama, Yo, Griffin, Aaron T., Vokes, Natalie I., Sakhi, Mustafa, Kamesan, Vashine, Rizvi, Hira, Ricciuti, Biagio, Forde, Patrick M., Anagnostou, Valsamo, Riess, Jonathan W., Gibbons, Don L., Pennell, Nathan A., Velcheti, Vamsidhar, Digumarthy, Subba R., Mino-Kenudson, Mari, Califano, Andrea, Heymach, John V., Herbst, Roy S., Brahmer, Julie R., Schalper, Kurt A., Velculescu, Victor E., Henick, Brian S., Rizvi, Naiyer, Jänne, Pasi A., Awad, Mark M., Chow, Andrew, Greenbaum, Benjamin D., Luksza, Marta, Shaw, Alice T., Wolchok, Jedd, Hacohen, Nir, Getz, Gad, and Gainor, Justin F.

Published
2023
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20. Targeting TBK1 to overcome resistance to cancer immunotherapy

Author

Sun, Yi, Revach, Or-yam, Anderson, Seth, Kessler, Emily A., Wolfe, Clara H., Jenney, Anne, Mills, Caitlin E., Robitschek, Emily J., Davis, Thomas G. R., Kim, Sarah, Fu, Amina, Ma, Xiang, Gwee, Jia, Tiwari, Payal, Du, Peter P., Sindurakar, Princy, Tian, Jun, Mehta, Arnav, Schneider, Alexis M., Yizhak, Keren, Sade-Feldman, Moshe, LaSalle, Thomas, Sharova, Tatyana, Xie, Hongyan, Liu, Shuming, Michaud, William A., Saad-Beretta, Rodrigo, Yates, Kathleen B., Iracheta-Vellve, Arvin, Spetz, Johan K. E., Qin, Xingping, Sarosiek, Kristopher A., Zhang, Gao, Kim, Jong Wook, Su, Mack Y., Cicerchia, Angelina M., Rasmussen, Martin Q., Klempner, Samuel J., Juric, Dejan, Pai, Sara I., Miller, David M., Giobbie-Hurder, Anita, Chen, Jonathan H., Pelka, Karin, Frederick, Dennie T., Stinson, Susanna, Ivanova, Elena, Aref, Amir R., Paweletz, Cloud P., Barbie, David A., Sen, Debattama R., Fisher, David E., Corcoran, Ryan B., Hacohen, Nir, Sorger, Peter K., Flaherty, Keith T., Boland, Genevieve M., Manguso, Robert T., and Jenkins, Russell W.

Published
2023
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21. Rationale and design of the Kidney Precision Medicine Project

Author

de Boer, Ian H, Alpers, Charles E, Azeloglu, Evren U, Balis, Ulysses GJ, Barasch, Jonathan M, Barisoni, Laura, Blank, Kristina N, Bomback, Andrew S, Brown, Keith, Dagher, Pierre C, Dighe, Ashveena L, Eadon, Michael T, El-Achkar, Tarek M, Gaut, Joseph P, Hacohen, Nir, He, Yongqun, Hodgin, Jeffrey B, Jain, Sanjay, Kellum, John A, Kiryluk, Krzysztof, Knight, Richard, Laszik, Zoltan G, Lienczewski, Chrysta, Mariani, Laura H, McClelland, Robyn L, Menez, Steven, Moledina, Dennis G, Mooney, Sean D, O’Toole, John F, Palevsky, Paul M, Parikh, Chirag R, Poggio, Emilio D, Rosas, Sylvia E, Rosengart, Matthew R, Sarwal, Minnie M, Schaub, Jennifer A, Sedor, John R, Sharma, Kumar, Steck, Becky, Toto, Robert D, Troyanskaya, Olga G, Tuttle, Katherine R, Vazquez, Miguel A, Waikar, Sushrut S, Williams, Kayleen, Wilson, Francis Perry, Zhang, Kun, Iyengar, Ravi, Kretzler, Matthias, Himmelfarb, Jonathan, Project, Kidney Precision Medicine, Lecker, Stewart, Stillman, Isaac, Waikar, Sushrut, Mcmahon, Gearoid, Weins, Astrid, Short, Samuel, Hoover, Paul, Aulisio, Mark, Cooperman, Leslie, Herlitz, Leal, O’Toole, John, Poggio, Emilio, Sedor, John, Jolly, Stacey, Appelbaum, Paul, Balderes, Olivia, Barasch, Jonathan, Bomback, Andrew, Canetta, Pietro A, d’Agati, Vivette D, Kudose, Satoru, Mehl, Karla, Radhakrishnan, Jai, Weng, Chenhua, Alexandrov, Theodore, Ashkar, Tarek, Barwinska, Daria, Dagher, Pierre, Dunn, Kenneth, Eadon, Michael, Ferkowicz, Michael, Kelly, Katherine, Sutton, Timothy, Winfree, Seth, Parikh, Chirag, Rosenberg, Avi, Villalobos, Pam, Malik, Rubab, Fine, Derek, Atta, Mohammed, Trujillo, Jose Manuel Monroy, Slack, Alison, Rosas, Sylvia, and Williams, Mark

Subjects
Clinical Research, Transplantation, Kidney Disease, Prevention, Renal and urogenital, Good Health and Well Being, Acute Kidney Injury, Adult, Humans, Kidney, Precision Medicine, Prospective Studies, Proteomics, Renal Insufficiency, Chronic, acute kidney injury, chronic kidney disease, diabetes, hypertension, precision medicine, Kidney Precision Medicine Project, Clinical Sciences, Urology & Nephrology
Abstract

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision-medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living-donor kidney biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomic analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for 10 years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

Published
2021

22. Molecular Signatures of Glomerular Neovascularization in a Patient with Diabetic Kidney Disease

Author

Ferkowicz, Michael J., Verma, Ashish, Barwinska, Daria, Melo Ferreira, Ricardo, Henderson, Joel M., Kirkpatrick, Mary, Silva, Paolo S., Steenkamp, Devin W., Phillips, Carrie L., Waikar, Sushrut S., Sutton, Timothy A., Lake, Blue, Zhang, Kun, Lecker, Stewart, Morales, Alexander, Stillman, Isaac, Bogen, Steve, Amodu, Afolarin A., Beck, Laurence, Henderson, Joel, Ilori, Titlayo, Maikhor, Shana, Onul, Ingrid, Schmidt, Insa, Verma, Ashish, Waikar, Sushrut, Yadati, Pranav, Yu, Guanghao, Colona, Mia R., McMahon, Gearoid, Weins, Astrid, Hacohen, Nir, Greka, Anna, Hoover, Paul J., Marshall, Jamie L., Aulisio, Mark, Bush, William, Chen, Yijiang, Crawford, Dana, Madabhushi, Anant, Viswanathan, Vidya S., Bush, Lakeshia, Cooperman, Leslie, Gadegbeku, Crystal, Herlitz, Leal, Jolly, Stacey, Nguyen, Jane, O’Malley, Charles, O’Toole, John, Palmer, Ellen, Poggio, Emilio, Spates-Harden, Kassandra, Sedor, John, Sendrey, Dianna, Taliercio, Jonathan, Appelbaum, Paul, Balderes, Olivia, Barasch, Jonathan, Berroue, Cecilia, Bomback, Andrew, Canetta, Pietro A., D’Agati, Vivette, Kiryluk, Krzysztof, Kudose, Satoru, Mehl, Karla, Sabatello, Maya, Shang, Ning, Varela, German, de Pinho Gonçalves, Joana, Lardenoije, Roy, Migas, Lukasz, Van de Plas, Raf, Barisoni, Laura, Rennke, Helmut, Azeloglu, Evren, Campbell, Kirk, Coca, Steven, He, Cijang, He, John, Iyengar, Srinivas Ravi, Lefferts, Seanee, Nadkarni, Girish, Patel, Marissa, Tokita, Joji, Ward, Stephen, Xiong, Yuguang, Verdoes, Abraham, Sabo, Angela, Barwinska, Daria, Gisch, Debora Lidia, Williams, James, Kelly, Katherine, Dunn, Kenneth, Asghari, Mahla, Eadon, Michael, Ferkowicz, Michael, Dagher, Pierre, Ferreira, Ricardo Melo, Winfree, Seth, Bledsoe, Sharon, Wofford, Stephanie, El-Achkar, Tarek, Sutton, Timothy, Bowen, William, Cheng, Ying-Hua, Slade, Austen, Record, Elizabeth, Cheng, Yinghua, Borner, Katy, Herr, Bruce, Jain, Yashvardhan, Quardokus, Ellen, Atta, Mohamed, Bernard, Lauren, Menez, Steven, Parikh, Chirag, Corona Villalobos, Celia Pamela, Wang, Ashley, Wen, Yumeng, Xu, Alan, Chen, Sarah, Donohoe, Isabel, Johansen, Camille, Rosas, Sylvia, Sun, Jennifer, Ardayfio, Joseph, Bebiak, Jack, Brown, Keith, Campbell, Taneisha, Fox, Monica, Hayashi, Lynda, Jefferson, Nichole, Richard Knight, Jennifer Jones, Koewler, Robert, Pinkeney, Roy, Saul, John, Shpigel, Anna, Stutzke, Christy, Prasad, Pottumarthi, Madhavan, Sethu M., Parikh, Samir, Rovin, Brad, Shapiro, John P., Anderton, Christopher, Lukowski, Jessica, Pasa-Tolic, Ljiljana, Velickovic, Dusan, Oliver, George, Mao, Weiguang, Sealfon, Rachel, Troyanskaya, Olga, Wong, Aaron, Pollack, Ari, Goltsev, Yury, Ginley, Brandon, Lutnick, Brendon, Anjani, Kavya, Laszik, Zoltan G., Mukatash, Tariq, Nolan, Garry, Beyda, David, Bracamonte, Erika, Brosius, Frank, Campos, Baltazar, Marquez, Nicole, Mendoza, Katherine, Scott, Raymond, Thajudeen, Bijin, Tsosie, Rebecca, Woodhead, Gregory, Saunders, Milda, Alloway, Rita R., Lee, Paul J., Rike, Adele, Shi, Tiffany, Woodle, E. Steve, Bjornstad, Petter, Hsieh, Elena, Kendrick, Jessica, Pyle, Laura, Thurman, Joshua, Vinovskis, Carissa, Wrobel, Julia, Lucarelli, Nicholas, Sarder, Pinaki, Bui, James, Carmona-Powell, Eunice, Gaba, Ron, Kelly, Tanika, Lash, James, Meza, Natalie, Redmond, Devona, Renteria, Amada, Ricardo, Ana, Setty, Suman, Srivastava, Anand, Alakwaa, Fadhl, Ascani, Heather, Balis, Ul, Bitzer, Markus, Blanc, Victoria, Bonevich, Nikki, Conser, Ninive, Demeke, Dawit, Dull, Rachel, Eddy, Sean, Frey, Renee, Hartman, John, He, Yongqun Oliver, Hodgin, Jeffrey, Kretzler, Matthias, Lienczewski, Chrysta, Luo, Jinghui, Mariani, Laura, McCown, Phillip, Menon, Rajasree, Nair, Viji, Otto, Edgar, Reamy, Rebecca, Rose, Michael, Schaub, Jennifer, Steck, Becky, Wright, Zachary, Coleman, Alyson, Henderson-Brown, Dorisann, Berge, Jerica, Caramori, Maria Luiza, Adeyi, Oyedele, Nachman, Patrick, Safadi, Sami, Flanagan, Siobhan, Ma, Sisi, Klett, Susan, Wolf, Susan, Harindhanavudhi, Tasma, Rao, Via, Bream, Peter, Froment, Anne, Kelley, Sara, Mottl, Amy, Roy-Chaudhury, Prabir, Zeitler, Evan, Bender, Filitsa, Elder, Michele, Gilliam, Matthew, Hall, Daniel E., Kellum, John A., Murugan, Raghavan, Palevsky, Paul, Rosengart, Matthew, Tan, Roderick, Tublin, Mitchell, Winters, James, Bansal, Shweta, Montellano, Richard, Pamreddy, Annapurna, Sharma, Kumar, Venkatachalam, Manjeri, Ye, Hongping, Zhang, Guanshi, Basit, Mujeeb, Cai, Qi, Hendricks, Allen, Hedayati, Susan, and Asra

Published
2024
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23. Participant Experience with Protocol Research Kidney Biopsies in the Kidney Precision Medicine Project

Author

Victoria-Castro, Angela M., Corona-Villalobos, Celia P., Xu, Alan Y., Onul, Ingrid, Huynh, Courtney, Chen, Sarah W., Ugwuowo, Ugochukwu, Sarkisova, Natalya, Dighe, Ashveena L., Blank, Kristina N., Blanc, Victoria M., Rose, Michael P., Himmelfarb, Jonathan, de Boer, Ian H., Tuttle, Katherine R., Roberts, Glenda V., Alexandrov, Theodore, Alloway, Rita R., Alpers, Charles E., Amodu, Afolarin A., Anderton, Christopher R., Anjani, Kavya, Appelbaum, Paul, Ardayfio, Joseph, Arora, Tanima, Ascani, Heather, El-Achkar, Tarek M., Aulisio, Mark, Azeloglu, Evren U., Balderes, Olivia, Balis, Ulysses G.J., Bansal, Shweta, Barasch, Jonathan M., Bansal, Shweta, Barkell, Alex, Barwinska, Daria, Basit, Mujeeb, Basta, Jeanine, Bebiak, Jack, Beck, Laurence H., Bender, Filitsa, Berglund, Ashley, Bernard, Lauren, Berrouet, Cecilia, Berry, Brooke, Bjornstad, Petter M., Blanc, Victoria M., Blank, Kristina N., Bledsoe, Sharon, Boada, Patrick, Bogen, Steve, Bomback, Andrew S., Bonevich, Nikole, Borner, Katy, Brown, Keith, Bueckle, Andreas, Burg, Ashley R., Burgess, Adam, Bush, Lakeshia, Bush, William S., Campbell, Catherine E., Campbell, Taneisha, Canetta, Pietro A., Cantley, Lloyd G., Caprioli, Richard M., Carson, Jonas, Chen, Sarah, Chen, Yijiang M., Cheng, Yinghua, Cimino, Jim, Colona, Mia R., Conser, Ninive C., Cooperman, Leslie, Crawford, Dana C., DʼAgati, Vivette D., Dagher, Pierre C., Daniel, Stephen, Daratha, Kenn, de Boer, Ian H., Diettman, Sabine M., Dighe, Ashveena L., Donohoe, Isabel, Dowd, Frederick, Dunn, Kenneth W., Eadon, Michael T., Eddy, Sean, Elder, Michele M., Ferkowicz, Michael J., Frey, Renee, Gadegbeku, Crystal A., Gaut, Joseph P., Gilliam, Matthew, Ginley, Brandon, Gisch, Debora, Goltsev, Yury, Gonzalez-Vicente, Agustin, Greka, Anna, Grewenow, Stephanie M., Hacohen, Nir, Hall, Daniel E., Hansen, Jens, Hayashi, Lynda, He, Cijang, He, Yougqun, Hedayati, S. Susan, Henderson, Joel M., Hendricks, Allen H., Herlitz, Leal, Herr, Bruce W., Himmelfarb, Jonathan, Hodgin, Jeffrey B., Hoofnagle, Andrew N., Hoover, Paul J., Ilori, Titlayo, Iyengar, Ravi, Jain, Sanjay, Jain, Yashvardhan, Janowczyk, Andrew, Jefferson, Nichole, Johansen, Camille, Jolly, Stacey, Kakade, Vijaykumar R., Kellum, John A., Kelly, Katherine J., Kermani, Asra, Kiryluk, Krzysztof, Knight, Richard, Koewler, Robert, Kretzler, Matthias, Kudose, Satoru, Lake, Blue B., Larson, Brandon, Laszik, Zoltan G., Lecker, Stewart H., Lee, Paul J., Lee, Simon C., Lienczewski, Chrysta, Limonte, Christine, Lu, Christopher Y., Lucarelli, Nicholas, Lukowski, Jessica, Luo, Jinghui, Lutnick, Brendon, Ma, Shihong, Madabhushi, Anant, Madhavan, Sethu M., Maikhor, Shana, Mariani, Laura H., Marshall, Jamie L., McClelland, Robyn L., McMahon, Gearoid M., Mehl, Karla, Ferreira, Ricardo Melo, Menez, Steven, Menon, Rajasree, Miller, R. Tyler, Moe, Orson W., Moledina, Dennis, Montellano, Richard, Mooney, Sean D., Morales, Martha Catalina, Mukatash, Tariq, Murugan, Raghavan, Nam, Yunbi, Nguyen, Jane, Nolan, Garry, Oʼtoole, John, Oliver, George (Holt), Onul, Ingrid, Otto, Edgar, Palevsky, Paul M., Palmer, Ellen, Pamreddy, Annapurna, Parikh, Chirag R., Parikh, Samir, Park, Christopher, Park, Harold, Pasa-Tolic, Ljiljana, Patel, Jiten, Patterson, Nathan, Phuong, Jim, Pillai, Anil, Pinkeney, Roy, Poggio, Emilio, Pollack, Ari, Prasad, Pottumarthi, Pyle, Laura, Quardokus, Ellen M., Randhawa, Parmjeet, Rauchman, Michael I., Record, Elizabeth, Rennke, Helmut, Rezaei, Kasra, Rike, Adele, Rivera, Marcelino, Roberts, Glenda V., Rosas, Sylvia E., Rosenberg, Avi, Rosengart, Matthew, Rovin, Brad, Roy, Neil, Sabatello, Maya, Sambandam, Kamalanathan, Sarder, Pinaki, Sarkisova, Natalya, Sarwal, Minnie, Saul, John, Schaub, Jennifer, Schmidt, Insa, Sealfon, Rachel, Sedor, John, Sendrey, Dianna, Shang, Ning, Shankland, Stuart, Shapiro, John P., Sharma, Kumar, Sharman, Kavya, Shaw, Melissa M., Shi, Tiffany, Shpigel, Anna, Sigdel, Tara, Slade, Austen, Snyder, Jamie, Spates-Harden, Kassandra, Spraggins, Jeffrey M., Srivastava, Anand, Steck, Becky, Stillman, Isaac, Stutzke, Christy, Su, Jing, Sun, Jennifer, Sutton, Timothy A., Taliercio, Jonathan, Tan, Roderick, Torrealba, Jose, Toto, Robert D., Troyanskaya, Olga, Tublin, Mitchell, Tuttle, Katherine R., Ugwuowo, Ugochukwu, Valerius, M. Todd, Van de Plas, Raf, Varela, German, Vazquez, Miguel, Velickovic, Dusan, Venkatachalam, Manjeri, Verma, Ashish, Victoria-Castro, Angela M., Vijayan, Anitha, Corona-Villalobos, Celia P., Vinovskis, Carissa, Viswanathan, Vidya S., Vita, Tina, Waikar, Sushrut, Wang, Ashley, Wang, Ruikang, Wang, Nancy, Weins, Astrid, Wen, Natasha, Wen, Yumeng, Wilcox, Adam, Williams, James C., Jr., Kayleen Williams, Williams, Mark, Wilson, Francis P., Winfree, Seth, Winters, James, Wofford, Stephanie, Wong, Aaron, Woodle, E. Steve, Xiong, Yuguang, Xu, Alan, Yadati, Pranav, Ye, Hongping, Yu, Guanghao, Zhang, Dianbo, Zhang, Guanshi, and Zhang, Kun

Published
2024
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24. Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses

Author

Lo, Jennifer A, Kawakubo, Masayoshi, Juneja, Vikram R, Su, Mack Y, Erlich, Tal H, LaFleur, Martin W, Kemeny, Lajos V, Rashid, Mamunur, Malehmir, Mohsen, Rabi, S Alireza, Raghavan, Rumya, Allouche, Jennifer, Kasumova, Gyulnara, Frederick, Dennie T, Pauken, Kristen E, Weng, Qing Yu, Pereira da Silva, Marcelo, Xu, Yu, van der Sande, Anita AJ, Silkworth, Whitney, Roider, Elisabeth, Browne, Edward P, Lieb, David J, Wang, Belinda, Garraway, Levi A, Wu, Catherine J, Flaherty, Keith T, Brinckerhoff, Constance E, Mullins, David W, Adams, David J, Hacohen, Nir, Hoang, Mai P, Boland, Genevieve M, Freeman, Gordon J, Sharpe, Arlene H, Manstein, Dieter, and Fisher, David E

Subjects
Cancer, Animals, Antigens, Neoplasm, Epitopes, Humans, Immune Checkpoint Inhibitors, Melanocytes, Melanoma, Mice, Biological Sciences, Medical and Health Sciences
Abstract

Although immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (PD-1), can deliver durable antitumor effects, most patients with cancer fail to respond. Recent studies suggest that ICI efficacy correlates with a higher load of tumor-specific neoantigens and development of vitiligo in patients with melanoma. Here, we report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes. Moreover, expansion of peripheral blood CD8+ T cell populations specific for melanocyte antigens was observed only in patients who responded to anti-PD-1 therapy, suggesting that ICI can promote breakdown of tolerance toward tumor-lineage self-antigens. In a mouse model of poorly immunogenic melanomas, spreading of epitope recognition toward wild-type melanocyte antigens was associated with markedly improved anti-PD-1 efficacy in two independent approaches: introduction of neoantigens by ultraviolet (UV) B radiation mutagenesis or the therapeutic combination of ablative fractional photothermolysis plus imiquimod. Complete responses against UV mutation-bearing tumors after anti-PD-1 resulted in protection from subsequent engraftment of melanomas lacking any shared neoantigens, as well as pancreatic adenocarcinomas forcibly overexpressing melanocyte-lineage antigens. Our data demonstrate that somatic mutations are sufficient to provoke strong antitumor responses after checkpoint blockade, but long-term responses are not restricted to these putative neoantigens. Epitope spreading toward T cell recognition of wild-type tumor-lineage self-antigens represents a common pathway for successful response to ICI, which can be evoked in neoantigen-deficient tumors by combination therapy with ablative fractional photothermolysis and imiquimod.

Published
2021

25. Combined PD-1, BRAF and MEK inhibition in BRAFV600E colorectal cancer: a phase 2 trial

Author

Tian, Jun, Chen, Jonathan H., Chao, Sherry X., Pelka, Karin, Giannakis, Marios, Hess, Julian, Burke, Kelly, Jorgji, Vjola, Sindurakar, Princy, Braverman, Jonathan, Mehta, Arnav, Oka, Tomonori, Huang, Mei, Lieb, David, Spurrell, Maxwell, Allen, Jill N., Abrams, Thomas A., Clark, Jeffrey W., Enzinger, Andrea C., Enzinger, Peter C., Klempner, Samuel J., McCleary, Nadine J., Meyerhardt, Jeffrey A., Ryan, David P., Yurgelun, Matthew B., Kanter, Katie, Van Seventer, Emily E., Baiev, Islam, Chi, Gary, Jarnagin, Joy, Bradford, William B., Wong, Edmond, Michel, Alexa G., Fetter, Isobel J., Siravegna, Giulia, Gemma, Angelo J., Sharpe, Arlene, Demehri, Shadmehr, Leary, Rebecca, Campbell, Catarina D., Yilmaz, Omer, Getz, Gad A., Parikh, Aparna R., Hacohen, Nir, and Corcoran, Ryan B.

Published
2023
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26. Accelerating Medicines Partnership: Organizational Structure and Preliminary Data From the Phase 1 Studies of Lupus Nephritis

Author

Hoover, Paul, Der, Evan, Berthier, Celine C, Arazi, Arnon, Lederer, James A, James, Judith A, Buyon, Jill, Petri, Michelle, Belmont, H Michael, Izmirly, Peter, Wofsy, David, Hacohen, Nir, Diamond, Betty, Putterman, Chaim, and Davidson, Anne

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Autoimmune Disease, Lupus, Kidney Disease, Clinical Research, Good Health and Well Being, Academic Medical Centers, Biomarkers, Clinical Trials, Phase I as Topic, Drug Industry, Humans, Lupus Nephritis, National Institutes of Health (U.S.), Preliminary Data, Public-Private Sector Partnerships, Sequence Analysis, RNA, United States, Public Health and Health Services, Psychology, Clinical sciences, Allied health and rehabilitation science
Abstract

The Accelerating Medicines Partnership (AMP) Lupus Network was established as a partnership between the National Institutes of Health, pharmaceutical companies, nonprofit stakeholders, and lupus investigators across multiple academic centers to apply high-throughput technologies to the analysis of renal tissue, urine, and blood from patients with lupus nephritis (LN). The AMP network provides publicly accessible data to the community with the goal of generating new scientific hypotheses and improving diagnostic and therapeutic tools so as to improve disease outcomes. We present here a description of the structure of the AMP Lupus Network and a summary of the preliminary results from the phase 1 studies. The successful completion of phase 1 sets the stage for analysis of a large cohort of LN samples in phase 2 and provides a model for establishing similar discovery cohorts.

Published
2020

27. B cells and tertiary lymphoid structures promote immunotherapy response

Author

Helmink, Beth A, Reddy, Sangeetha M, Gao, Jianjun, Zhang, Shaojun, Basar, Rafet, Thakur, Rohit, Yizhak, Keren, Sade-Feldman, Moshe, Blando, Jorge, Han, Guangchun, Gopalakrishnan, Vancheswaran, Xi, Yuanxin, Zhao, Hao, Amaria, Rodabe N, Tawbi, Hussein A, Cogdill, Alex P, Liu, Wenbin, LeBleu, Valerie S, Kugeratski, Fernanda G, Patel, Sapna, Davies, Michael A, Hwu, Patrick, Lee, Jeffrey E, Gershenwald, Jeffrey E, Lucci, Anthony, Arora, Reetakshi, Woodman, Scott, Keung, Emily Z, Gaudreau, Pierre-Olivier, Reuben, Alexandre, Spencer, Christine N, Burton, Elizabeth M, Haydu, Lauren E, Lazar, Alexander J, Zapassodi, Roberta, Hudgens, Courtney W, Ledesma, Deborah A, Ong, SuFey, Bailey, Michael, Warren, Sarah, Rao, Disha, Krijgsman, Oscar, Rozeman, Elisa A, Peeper, Daniel, Blank, Christian U, Schumacher, Ton N, Butterfield, Lisa H, Zelazowska, Monika A, McBride, Kevin M, Kalluri, Raghu, Allison, James, Petitprez, Florent, Fridman, Wolf Herman, Sautès-Fridman, Catherine, Hacohen, Nir, Rezvani, Katayoun, Sharma, Padmanee, Tetzlaff, Michael T, Wang, Linghua, and Wargo, Jennifer A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Immunization, Cancer, Vaccine Related, Genetics, B-Lymphocytes, Biomarkers, Tumor, Carcinoma, Renal Cell, Cell Cycle Checkpoints, Clone Cells, Dendritic Cells, Follicular, Gene Expression Regulation, Neoplastic, Humans, Immunologic Memory, Immunotherapy, Mass Spectrometry, Melanoma, Neoplasm Metastasis, Phenotype, Prognosis, RNA-Seq, Receptors, Immunologic, Single-Cell Analysis, T-Lymphocytes, Tertiary Lymphoid Structures, Transcriptome, General Science & Technology
Abstract

Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1-10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11-15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.

Published
2020

28. In vivo CRISPR screens reveal the landscape of immune evasion pathways across cancer

Author

Dubrot, Juan, Du, Peter P., Lane-Reticker, Sarah Kate, Kessler, Emily A., Muscato, Audrey J., Mehta, Arnav, Freeman, Samuel S., Allen, Peter M., Olander, Kira E., Ockerman, Kyle M., Wolfe, Clara H., Wiesmann, Fabius, Knudsen, Nelson H., Tsao, Hsiao-Wei, Iracheta-Vellve, Arvin, Schneider, Emily M., Rivera-Rosario, Andrea N., Kohnle, Ian C., Pope, Hans W., Ayer, Austin, Mishra, Gargi, Zimmer, Margaret D., Kim, Sarah Y., Mahapatra, Animesh, Ebrahimi-Nik, Hakimeh, Frederick, Dennie T., Boland, Genevieve M., Haining, W. Nicholas, Root, David E., Doench, John G., Hacohen, Nir, Yates, Kathleen B., and Manguso, Robert T.

Published
2022
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30. The Human Cell Atlas White Paper

Author

Regev, Aviv, Teichmann, Sarah, Rozenblatt-Rosen, Orit, Stubbington, Michael, Ardlie, Kristin, Amit, Ido, Arlotta, Paola, Bader, Gary, Benoist, Christophe, Biton, Moshe, Bodenmiller, Bernd, Bruneau, Benoit, Campbell, Peter, Carmichael, Mary, Carninci, Piero, Castelo-Soccio, Leslie, Clatworthy, Menna, Clevers, Hans, Conrad, Christian, Eils, Roland, Freeman, Jeremy, Fugger, Lars, Goettgens, Berthold, Graham, Daniel, Greka, Anna, Hacohen, Nir, Haniffa, Muzlifah, Helbig, Ingo, Heuckeroth, Robert, Kathiresan, Sekar, Kim, Seung, Klein, Allon, Knoppers, Bartha, Kriegstein, Arnold, Lander, Eric, Lee, Jane, Lein, Ed, Linnarsson, Sten, Macosko, Evan, MacParland, Sonya, Majovski, Robert, Majumder, Partha, Marioni, John, McGilvray, Ian, Merad, Miriam, Mhlanga, Musa, Naik, Shalin, Nawijn, Martijn, Nolan, Garry, Paten, Benedict, Pe'er, Dana, Philippakis, Anthony, Ponting, Chris, Quake, Steve, Rajagopal, Jayaraj, Rajewsky, Nikolaus, Reik, Wolf, Rood, Jennifer, Saeb-Parsy, Kourosh, Schiller, Herbert, Scott, Steve, Shalek, Alex, Shapiro, Ehud, Shin, Jay, Skeldon, Kenneth, Stratton, Michael, Streicher, Jenna, Stunnenberg, Henk, Tan, Kai, Taylor, Deanne, Thorogood, Adrian, Vallier, Ludovic, van Oudenaarden, Alexander, Watt, Fiona, Weicher, Wilko, Weissman, Jonathan, Wells, Andrew, Wold, Barbara, Xavier, Ramnik, Zhuang, Xiaowei, and Committee, Human Cell Atlas Organizing

Subjects
Quantitative Biology - Tissues and Organs
Abstract

The Human Cell Atlas (HCA) will be made up of comprehensive reference maps of all human cells - the fundamental units of life - as a basis for understanding fundamental human biological processes and diagnosing, monitoring, and treating disease. It will help scientists understand how genetic variants impact disease risk, define drug toxicities, discover better therapies, and advance regenerative medicine. A resource of such ambition and scale should be built in stages, increasing in size, breadth, and resolution as technologies develop and understanding deepens. We will therefore pursue Phase 1 as a suite of flagship projects in key tissues, systems, and organs. We will bring together experts in biology, medicine, genomics, technology development and computation (including data analysis, software engineering, and visualization). We will also need standardized experimental and computational methods that will allow us to compare diverse cell and tissue types - and samples across human communities - in consistent ways, ensuring that the resulting resource is truly global. This document, the first version of the HCA White Paper, was written by experts in the field with feedback and suggestions from the HCA community, gathered during recent international meetings. The White Paper, released at the close of this yearlong planning process, will be a living document that evolves as the HCA community provides additional feedback, as technological and computational advances are made, and as lessons are learned during the construction of the atlas.

Published
2018

31. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry

Author

Zhang, Fan, Wei, Kevin, Slowikowski, Kamil, Fonseka, Chamith Y, Rao, Deepak A, Kelly, Stephen, Goodman, Susan M, Tabechian, Darren, Hughes, Laura B, Salomon-Escoto, Karen, Watts, Gerald FM, Jonsson, A Helena, Rangel-Moreno, Javier, Meednu, Nida, Rozo, Cristina, Apruzzese, William, Eisenhaure, Thomas M, Lieb, David J, Boyle, David L, Mandelin, Arthur M, Boyce, Brendan F, DiCarlo, Edward, Gravallese, Ellen M, Gregersen, Peter K, Moreland, Larry, Firestein, Gary S, Hacohen, Nir, Nusbaum, Chad, Lederer, James A, Perlman, Harris, Pitzalis, Costantino, Filer, Andrew, Holers, V Michael, Bykerk, Vivian P, Donlin, Laura T, Anolik, Jennifer H, Brenner, Michael B, and Raychaudhuri, Soumya

Subjects
Clinical Research, Autoimmune Disease, Arthritis, Human Genome, Rheumatoid Arthritis, Genetics, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Arthritis, Rheumatoid, Autoimmunity, Biomarkers, Computational Biology, Cross-Sectional Studies, Cytokines, Fibroblasts, Flow Cytometry, Gene Expression, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Histocompatibility Antigens Class II, Humans, Leukocytes, Monocytes, Signal Transduction, Single-Cell Analysis, Synovial Membrane, T-Lymphocyte Subsets, Transcriptome, Workflow, Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Immunology
Abstract

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

Published
2019

32. The immune cell landscape in kidneys of patients with lupus nephritis

Author

Arazi, Arnon, Rao, Deepak A, Berthier, Celine C, Davidson, Anne, Liu, Yanyan, Hoover, Paul J, Chicoine, Adam, Eisenhaure, Thomas M, Jonsson, A Helena, Li, Shuqiang, Lieb, David J, Zhang, Fan, Slowikowski, Kamil, Browne, Edward P, Noma, Akiko, Sutherby, Danielle, Steelman, Scott, Smilek, Dawn E, Tosta, Patti, Apruzzese, William, Massarotti, Elena, Dall’Era, Maria, Park, Meyeon, Kamen, Diane L, Furie, Richard A, Payan-Schober, Fernanda, Pendergraft, William F, McInnis, Elizabeth A, Buyon, Jill P, Petri, Michelle A, Putterman, Chaim, Kalunian, Kenneth C, Woodle, E Steve, Lederer, James A, Hildeman, David A, Nusbaum, Chad, Raychaudhuri, Soumya, Kretzler, Matthias, Anolik, Jennifer H, Brenner, Michael B, Wofsy, David, Hacohen, Nir, and Diamond, Betty

Subjects
Lupus, Genetics, Autoimmune Disease, Kidney Disease, Clinical Research, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, Inflammatory and immune system, Renal and urogenital, Biomarkers, Biopsy, Cluster Analysis, Computational Biology, Epithelial Cells, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Humans, Immunophenotyping, Interferons, Kidney, Leukocytes, Lupus Nephritis, Lymphocytes, Molecular Sequence Annotation, Myeloid Cells, Single-Cell Analysis, Transcriptome, Accelerating Medicines Partnership in SLE network, Immunology
Abstract

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.

Published
2019

33. Genetic analysis of isoform usage in the human anti-viral response reveals influenza-specific regulation of ERAP2 transcripts under balancing selection

Author

Ye, Chun Jimmie, Chen, Jenny, Villani, Alexandra-Chloé, Gate, Rachel E, Subramaniam, Meena, Bhangale, Tushar, Lee, Mark N, Raj, Towfique, Raychowdhury, Raktima, Li, Weibo, Rogel, Noga, Simmons, Sean, Imboywa, Selina H, Chipendo, Portia I, McCabe, Cristin, Lee, Michelle H, Frohlich, Irene Y, Stranger, Barbara E, De Jager, Philip L, Regev, Aviv, Behrens, Tim, and Hacohen, Nir

Subjects
Biological Sciences, Genetics, Infectious Diseases, Biotechnology, Human Genome, Pneumonia & Influenza, Influenza, Aetiology, 2.1 Biological and endogenous factors, Infection, Adolescent, Adult, Alternative Splicing, Aminopeptidases, Chromosome Mapping, Computational Biology, Dendritic Cells, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Ontology, Genetic Predisposition to Disease, Genetic Testing, Genetic Variation, Host-Pathogen Interactions, Humans, Influenza A virus, Influenza, Human, Interferon Type I, Male, Middle Aged, Models, Biological, Molecular Sequence Annotation, Monocytes, Quantitative Trait Loci, Transcriptome, Young Adult, Medical and Health Sciences, Bioinformatics
Abstract

While genetic variants are known to be associated with overall gene abundance in stimulated immune cells, less is known about their effects on alternative isoform usage. By analyzing RNA-seq profiles of monocyte-derived dendritic cells from 243 individuals, we uncovered thousands of unannotated isoforms synthesized in response to influenza infection and type 1 interferon stimulation. We identified more than a thousand quantitative trait loci (QTLs) associated with alternate isoform usage (isoQTLs), many of which are independent of expression QTLs (eQTLs) for the same gene. Compared with eQTLs, isoQTLs are enriched for splice sites and untranslated regions, but depleted of sequences upstream of annotated transcription start sites. Both eQTLs and isoQTLs explain a significant proportion of the disease heritability attributed to common genetic variants. At the ERAP2 locus, we shed light on the function of the gene and how two frequent, highly differentiated haplotypes with intermediate frequencies could be maintained by balancing selection. At baseline and following type 1 interferon stimulation, the major haplotype is associated with low ERAP2 expression caused by nonsense-mediated decay, while the minor haplotype, known to increase Crohn's disease risk, is associated with high ERAP2 expression. In response to influenza infection, we found two uncharacterized isoforms expressed from the major haplotype, likely the result of multiple perfectly linked variants affecting the transcription and splicing at the locus. Thus, genetic variants at a single locus could modulate independent gene regulatory processes in innate immune responses and, in the case of ERAP2, may confer a historical fitness advantage in response to virus.

Published
2018

34. Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients

Author

LaSalle, Thomas J., Gonye, Anna L.K., Freeman, Samuel S., Kaplonek, Paulina, Gushterova, Irena, Kays, Kyle R., Manakongtreecheep, Kasidet, Tantivit, Jessica, Rojas-Lopez, Maricarmen, Russo, Brian C., Sharma, Nihaarika, Thomas, Molly F., Lavin-Parsons, Kendall M., Lilly, Brendan M., Mckaig, Brenna N., Charland, Nicole C., Khanna, Hargun K., Lodenstein, Carl L., Margolin, Justin D., Blaum, Emily M., Lirofonis, Paola B., Revach, Or-Yam, Mehta, Arnav, Sonny, Abraham, Bhattacharyya, Roby P., Parry, Blair Alden, Goldberg, Marcia B., Alter, Galit, Filbin, Michael R., Villani, Alexandra-Chloé, Hacohen, Nir, and Sade-Feldman, Moshe

Published
2022
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35. Landscape of helper and regulatory antitumour CD4+ T cells in melanoma

Author

Oliveira, Giacomo, Stromhaug, Kari, Cieri, Nicoletta, Iorgulescu, J. Bryan, Klaeger, Susan, Wolff, Jacquelyn O., Rachimi, Suzanna, Chea, Vipheaviny, Krause, Kate, Freeman, Samuel S., Zhang, Wandi, Li, Shuqiang, Braun, David A., Neuberg, Donna, Carr, Steven A., Livak, Kenneth J., Frederick, Dennie T., Fritsch, Edward F., Wind-Rotolo, Megan, Hacohen, Nir, Sade-Feldman, Moshe, Yoon, Charles H., Keskin, Derin B., Ott, Patrick A., Rodig, Scott J., Boland, Genevieve M., and Wu, Catherine J.

Published
2022
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37. Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4+ T cell response.

Author

Chudnovskiy, Aleksey, Castro, Tiago B. R., Nakandakari-Higa, Sandra, Cui, Ang, Lin, Chia-Hao, Sade-Feldman, Moshe, Phillips, Brooke K., Pae, Juhee, Mesin, Luka, Bortolatto, Juliana, Schweitzer, Lawrence D., Pasqual, Giulia, Lu, Li-Fan, Hacohen, Nir, and Victora, Gabriel D.

Subjects
T helper cells, T cells, TUMOR antigens, NATURAL immunity, DENDRITIC cells
Abstract

Dendritic cells (DCs) are uniquely capable of transporting tumor antigens to tumor-draining lymph nodes (tdLNs) and interact with effector T cells in the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)–based single-cell transcriptomics, we identified individual DCs capable of presenting antigen to CD4+ T cells in both the tdLN and TME. Our findings revealed that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both in tumors and in the tdLN and that checkpoint blockade drugs enhance these interactions. These findings show that a relatively small fraction of DCs is responsible for most of the antigen presentation in the tdLN and TME to both CD4+ and CD8+ tumor–specific T cells and that classical checkpoint blockade enhances CD40-driven DC activation at both sites. Editor's summary: Dendritic cells (DCs) are critical for generating antitumor T cell responses, including after immune checkpoint blockade, but the features of specific DCs involved in this process are not well defined. Using LIPSTIC proximity–based labeling in combination with single-cell transcriptomics, Chudnovskiy et al. characterized individual DCs presenting tumor-derived antigen in a mouse model of melanoma. In tumor-draining lymph nodes, antigen-presenting DCs constituted less than 15% of all DCs and adopted a hyperactivated phenotype characterized by IL-27 production. In tumors, T cell–interacting DCs adopted a similar, albeit less mature, transcriptional state. Interactions between DCs and T cells were enhanced by anti–CTLA-4 immune checkpoint blockade, highlighting the importance of these contacts in driving antitumor immune responses. —Claire Olingy [ABSTRACT FROM AUTHOR]

Published
2024
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38. Intrahepatic plasma cells, but not atypical memory B cells, associate with clinical phases of chronic hepatitis B.

Author

Osmani, Zgjim, Villanueva, Martin Arreola, Joseph‐Chazan, Jasmin, Beudeker, Boris J., de Knegt, Robert J., Chung, Raymond T., Hacohen, Nir, Aerssens, Jeroen, Bollekens, Jacques, Janssen, Harry L. A., Gehring, Adam J., Lauer, Georg M., Shalek, Alex K., van de Werken, Harmen J. G., and Boonstra, Andre

Abstract

Studies have traditionally focused on the role of T cells in chronic hepatitis B (CHB), but recent evidence supports a role for B cells. The enrichment of so‐called atypical memory (AtM) B cells, which show reduced signaling and impaired differentiation, is believed to be a characteristic feature of CHB, potentially contributing to the observed dysfunctional anti‐HBsAg B‐cell responses. Our study, involving 62 CHB patients across clinical phases, identified AtM B cells expressing IFNLR1 and interferon‐stimulated genes. Contrary to previous reports, we found relatively low frequencies of AtM B cells in the liver, comparable to peripheral blood. However, liver plasma cell frequencies were significantly higher, particularly during phases with elevated viral loads and liver enzyme levels. Liver plasma cells exhibited signs of active proliferation, especially in the immune active phase. Our findings suggest a potential role for plasma cells, alongside potential implications and consequences of local proliferation, within the livers of CHB patients. While the significance of AtM B cells remains uncertain, further investigation is warranted to determine their responsiveness to interferons and their role in CHB. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer

Author

Ouspenskaia, Tamara, Law, Travis, Clauser, Karl R., Klaeger, Susan, Sarkizova, Siranush, Aguet, François, Li, Bo, Christian, Elena, Knisbacher, Binyamin A., Le, Phuong M., Hartigan, Christina R., Keshishian, Hasmik, Apffel, Annie, Oliveira, Giacomo, Zhang, Wandi, Chen, Sarah, Chow, Yuen Ting, Ji, Zhe, Jungreis, Irwin, Shukla, Sachet A., Justesen, Sune, Bachireddy, Pavan, Kellis, Manolis, Getz, Gad, Hacohen, Nir, Keskin, Derin B., Carr, Steven A., Wu, Catherine J., and Regev, Aviv

Published
2022
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40. Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue

Author

Donlin, Laura T, Rao, Deepak A, Wei, Kevin, Slowikowski, Kamil, McGeachy, Mandy J, Turner, Jason D, Meednu, Nida, Mizoguchi, Fumitaka, Gutierrez-Arcelus, Maria, Lieb, David J, Keegan, Joshua, Muskat, Kaylin, Hillman, Joshua, Rozo, Cristina, Ricker, Edd, Eisenhaure, Thomas M, Li, Shuqiang, Browne, Edward P, Chicoine, Adam, Sutherby, Danielle, Noma, Akiko, Accelerating Medicines Partnership RA/SLE Network, Nusbaum, Chad, Kelly, Stephen, Pernis, Alessandra B, Ivashkiv, Lionel B, Goodman, Susan M, Robinson, William H, Utz, Paul J, Lederer, James A, Gravallese, Ellen M, Boyce, Brendan F, Hacohen, Nir, Pitzalis, Costantino, Gregersen, Peter K, Firestein, Gary S, Raychaudhuri, Soumya, Moreland, Larry W, Holers, V Michael, Bykerk, Vivian P, Filer, Andrew, Boyle, David L, Brenner, Michael B, and Anolik, Jennifer H

Subjects
Accelerating Medicines Partnership RA/SLE Network, Synovial Membrane, Humans, Arthritis, Rheumatoid, Cryopreservation, Flow Cytometry, High-Throughput Screening Assays, Accelerating Medicines Partnership, Arthroplasty, CyTOF, Mass cytometry, RNA sequencing, Rheumatoid arthritis, Synovial biopsy, Synovial tissue, Arthritis, Autoimmune Disease, Biotechnology, Human Genome, Clinical Research, Genetics, Bioengineering, 2.1 Biological and endogenous factors, Inflammatory and immune system, Arthritis & Rheumatology, Clinical Sciences, Immunology, Public Health and Health Services
Abstract

BackgroundDetailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples.MethodsMultiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq.ResultsUpon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4+ and CD8+ T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified.ConclusionsWe have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers.

Published
2018

41. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

Author

Baillie, J Kenneth, Bretherick, Andrew, Haley, Christopher S, Clohisey, Sara, Gray, Alan, Neyton, Lucile PA, Barrett, Jeffrey, Stahl, Eli A, Tenesa, Albert, Andersson, Robin, Brown, J Ben, Faulkner, Geoffrey J, Lizio, Marina, Schaefer, Ulf, Daub, Carsten, Itoh, Masayoshi, Kondo, Naoto, Lassmann, Timo, Kawai, Jun, IIBDGC Consortium, Mole, Damian, Bajic, Vladimir B, Heutink, Peter, Rehli, Michael, Kawaji, Hideya, Sandelin, Albin, Suzuki, Harukazu, Satsangi, Jack, Wells, Christine A, Hacohen, Nir, Freeman, Thomas C, Hayashizaki, Yoshihide, Carninci, Piero, Forrest, Alistair RR, and Hume, David A

Subjects
IIBDGC Consortium, Humans, Crohn Disease, Genetic Predisposition to Disease, Gene Expression Profiling, Genomics, Databases, Genetic, Promoter Regions, Genetic, Transcriptome, Databases, Genetic, Promoter Regions, Mathematical Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

Published
2018

42. The Human Cell Atlas.

Author

Regev, Aviv, Teichmann, Sarah A, Lander, Eric S, Amit, Ido, Benoist, Christophe, Birney, Ewan, Bodenmiller, Bernd, Campbell, Peter, Carninci, Piero, Clatworthy, Menna, Clevers, Hans, Deplancke, Bart, Dunham, Ian, Eberwine, James, Eils, Roland, Enard, Wolfgang, Farmer, Andrew, Fugger, Lars, Göttgens, Berthold, Hacohen, Nir, Haniffa, Muzlifah, Hemberg, Martin, Kim, Seung, Klenerman, Paul, Kriegstein, Arnold, Lein, Ed, Linnarsson, Sten, Lundberg, Emma, Lundeberg, Joakim, Majumder, Partha, Marioni, John C, Merad, Miriam, Mhlanga, Musa, Nawijn, Martijn, Netea, Mihai, Nolan, Garry, Pe'er, Dana, Phillipakis, Anthony, Ponting, Chris P, Quake, Stephen, Reik, Wolf, Rozenblatt-Rosen, Orit, Sanes, Joshua, Satija, Rahul, Schumacher, Ton N, Shalek, Alex, Shapiro, Ehud, Sharma, Padmanee, Shin, Jay W, Stegle, Oliver, Stratton, Michael, Stubbington, Michael JT, Theis, Fabian J, Uhlen, Matthias, van Oudenaarden, Alexander, Wagner, Allon, Watt, Fiona, Weissman, Jonathan, Wold, Barbara, Xavier, Ramnik, Yosef, Nir, and Human Cell Atlas Meeting Participants

Subjects
Human Cell Atlas Meeting Participants, Eukaryotic Cells, Humans, Human Body, International Cooperation, Atlases as Topic, cell atlas, cell biology, computational biology, human, lineage, mouse, science forum, single-cell genomics, systems biology, Biochemistry and Cell Biology
Abstract

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

Published
2017

43. Specific oncogene activation of the cell of origin in mucosal melanoma

Author

Babu, Swathy, primary, Chen, Jiajia, additional, Robitschek, Emily, additional, Baron, Chloe S., additional, McConnell, Alicia, additional, Wu, Constance, additional, Dedeilia, Aikaterini, additional, Sade-Feldman, Moshe, additional, Modhurima, Rodsy, additional, Manos, Michael P., additional, Chen, Kevin Y., additional, Cox, Anna M., additional, Ludwig, Calvin G., additional, Yang, Jiekun, additional, Kellis, Manolis, additional, Buchbinder, Elizabeth I., additional, Hacohen, Nir, additional, Boland, Genevieve M., additional, Abraham, Brian J., additional, Liu, David, additional, Zon, Leonard I., additional, and Insco, Megan L., additional

Published
2024
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46. Cadherin-11, Sparc-related modular calcium binding protein-2, and Pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis

Author

Knight, Richard, Lecker, Stewart H., Stillman, Isaac, Bogen, Steve, Amodu, Afolarin A., Ilori, Titlayo, Maikhor, Shana, Schmidt, Insa M., Beck, Laurence H., Henderson, Joel M., Onul, Ingrid, Verma, Ashish, McMahon, Gearoid M., Valerius, M. Todd, Waikar, Sushrut, Weins, Astrid, Colona, Mia R., Greka, Anna, Hacohen, Nir, Hoover, Paul J., Marshall, Jamie L., Aulisio, Mark, Chen, Yijiang M., Janowczyk, Andrew, Jayapandian, Catherine, Viswanathan, Vidya S., Bush, William S., Crawford, Dana C., Madabhushi, Anant, Bush, Lakeshia, Cooperman, Leslie, Gonzalez-Vicente, Agustin, Herlitz, Leal, Jolly, Stacey, Nguyen, Jane, O’toole, John, Palmer, Ellen, Poggio, Emilio, Sedor, John, Sendrey, Dianna, Spates-Harden, Kassandra, Taliercio, Jonathan, Bjornstad, Petter M., Pyle, Laura, Vinovskis, Carissa, Appelbaum, Paul, Balderes, Olivia, Barasch, Jonathan M., Bomback, Andrew S., Canetta, Pietro A., D’Agati, Vivette D., Kiryluk, Krzysztof, Kudose, Satoru, Mehl, Karla, Shang, Ning, Bansal, Shweta, Alexandrov, Theodore, Rennke, Helmut, El-Achkar, Tarek M., Barwinska, Daria, Bledso, Sharon, Borner, Katy, Bueckle, Andreas, Cheng, Yinghua, Dagher, Pierre C., Dunn, Kenneth W., Eadon, Michael T., Ferkowicz, Michael J., Herr, Bruce W., Kelly, Katherine J., Ferreira, Ricardo Melo, Quardokus, Ellen M., Record, Elizabeth, Rivera, Marcelino, Su, Jing, Sutton, Timothy A., Williams, James C., Jr., Winfree, Seth, Jain, Yashvardhan, Menez, Steven, Parikh, Chirag R., Rosenberg, Avi, Corona-Villalobos, Celia P., Wen, Yumeng, Johansen, Camille, Rosas, Sylvia E., Roy, Neil, Sun, Jennifer, Williams, Mark, Azeloglu, Evren U., Hansen, Jens, He, Cijang, Iyengar, Ravi, Xiong, Yuguang, Prasad, Pottumarthi, Srivastava, Anand, Madhavan, Sethu M., Parikh, Samir, Rovin, Brad, Shapiro, John P., Anderton, Christopher R., Lukowski, Jessica, Pasa-Tolic, Ljiljana, Velickovic, Dusan, Oliver, George (Holt), Ardayfio, Joseph, Bebiak, Jack, Brown, Keith, Campbell, Taneisha, Campbell, Catherine E., Hayashi, Lynda, Jefferson, Nichole, Roberts, Glenda V., Saul, John, Shpigel, Anna, Stutzke, Christy, Koewler, Robert, Pinkeney, Roy, Sealfon, Rachel, Troyanskaya, Olga, Wong, Aaron, Tuttle, Katherine R., Pollack, Ari, Goltsev, Yury, Ginley, Brandon, Lucarelli, Nicholas, Lutnick, Brendon, Sarder, Pinaki, Lake, Blue B., Zhang, Kun, Boada, Patrick, Laszik, Zoltan G., Nolan, Garry, Anjani, Kavya, Sarwal, Minnie, Mukatash, Tariq, Sigdel, Tara, Alloway, Rita R., Burg, Ashley R., Lee, Paul J., Rike, Adele, Shi, Tiffany, Woodle, E. Steve, Ascani, Heather, Balis, Ulysses G.J., Blanc, Victoria M., Conser, Ninive C., Eddy, Sean, Frey, Renee, He, Yougqun, Hodgin, Jeffrey B., Kretzler, Matthias, Lienczewski, Chrysta, Luo, Jinghui, Mariani, Laura H., Menon, Rajasree, Otto, Edgar, Schaub, Jennifer, Steck, Becky, Elder, Michele M., Gilliam, Matthew, Hall, Daniel E., Murugan, Raghavan, Palevsky, Paul M., Randhawa, Parmjeet, Rosengart, Matthew, Tublin, Mitchell, Vita, Tina, Winters, James, Kellum, John A., Alpers, Charles E., Berglund, Ashley, Berry, Brooke, Blank, Kristina N., Carson, Jonas, Daniel, Stephen, De Boer, Ian H., Dighe, Ashveena L., Dowd, Frederick, Grewenow, Stephanie M., Himmelfarb, Jonathan, Hoofnagle, Andrew N., Limonte, Christine, McClelland, Robyn L., Mooney, Sean D., Rezaei, Kasra, Shankland, Stuart, Snyder, Jamie, Wang, Ruikang, Wilcox, Adam, Williams, Kayleen, Park, Christopher, Montellano, Richard, Pamreddy, Annapurna, Sharma, Kumar, Venkatachalam, Manjeri, Ye, Hongping, Zhang, Guanshi, Basit, Mujeeb, Hedayati, S. Susan, Kermani, Asra, Lee, Simon C., Lu, Christopher Y., Miller, R. Tyler, Moe, Orson W., Patel, Jiten, Pillai, Anil, Sambandam, Kamalanathan, Torrealba, Jose, Toto, Robert D., Vazquez, Miguel, Wang, Nancy, Wen, Natasha, Zhang, Dianbo, Park, Harold, Caprioli, Richard M., Patterson, Nathan, Sharman, Kavya, Spraggins, Jeffrey M., Van de Plas, Raf, Basta, Jeanine, Diettman, Sabine M., Gaut, Joseph P., Jain, Sanjay, Rauchman, Michael I., Vijayan, Anitha, Cantley, Lloyd G., Kakade, Vijaykumar R., Moledina, Dennis, Shaw, Melissa M., Ugwuowo, Ugochukwu, Wilson, Francis P., Arora, Tanima, Kestenbaum, Bryan R., Alexopoulos, Leonidas G., Palsson, Ragnar, Liu, Jing, Stillman, Isaac E., Rennke, Helmut G., Vaidya, Vishal S., Wu, Haojia, Humphreys, Benjamin D., and Waikar, Sushrut S.

Published
2021
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47. Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial

Author

Parikh, Aparna R., Szabolcs, Annamaria, Allen, Jill N., Clark, Jeffrey W., Wo, Jennifer Y., Raabe, Michael, Thel, Hannah, Hoyos, David, Mehta, Arnav, Arshad, Sanya, Lieb, David J., Drapek, Lorraine C., Blaszkowsky, Lawrence S., Giantonio, Bruce J., Weekes, Colin D., Zhu, Andrew X., Goyal, Lipika, Nipp, Ryan D., Dubois, Jon S., Van Seventer, Emily E., Foreman, Bronwen E., Matlack, Lauren E., Ly, Leilana, Meurer, Jessica A., Hacohen, Nir, Ryan, David P., Yeap, Beow Y., Corcoran, Ryan B., Greenbaum, Benjamin D., Ting, David T., and Hong, Theodore S.

Published
2021
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48. Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

Author

Lavin-Parsons, Kendall, Parry, Blair, Lilley, Brendan, Lodenstein, Carl, McKaig, Brenna, Charland, Nicole, Khanna, Hargun, Margolin, Justin, Gonye, Anna, Gushterova, Irena, Lasalle, Tom, Sharma, Nihaarika, Russo, Brian C., Rojas-Lopez, Maricarmen, Sade-Feldman, Moshe, Manakongtreecheep, Kasidet, Tantivit, Jessica, Fisher Thomas, Molly, Weingarten-Gabbay, Shira, Klaeger, Susan, Sarkizova, Siranush, Pearlman, Leah R., Chen, Da-Yuan, Gallagher, Kathleen M.E., Bauer, Matthew R., Taylor, Hannah B., Dunn, W. Augustine, Tarr, Christina, Sidney, John, Rachimi, Suzanna, Conway, Hasahn L., Katsis, Katelin, Wang, Yuntong, Leistritz-Edwards, Del, Durkin, Melissa R., Tomkins-Tinch, Christopher H., Finkel, Yaara, Nachshon, Aharon, Gentili, Matteo, Rivera, Keith D., Carulli, Isabel P., Chea, Vipheaviny A., Chandrashekar, Abishek, Bozkus, Cansu Cimen, Carrington, Mary, Bhardwaj, Nina, Barouch, Dan H., Sette, Alessandro, Maus, Marcela V., Rice, Charles M., Clauser, Karl R., Keskin, Derin B., Pregibon, Daniel C., Hacohen, Nir, Carr, Steven A., Abelin, Jennifer G., Saeed, Mohsan, and Sabeti, Pardis C.

Published
2021
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49. Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions

Author

Filbin, Michael R., Mehta, Arnav, Schneider, Alexis M., Kays, Kyle R., Guess, Jamey R., Gentili, Matteo, Fenyves, Bánk G., Charland, Nicole C., Gonye, Anna L.K., Gushterova, Irena, Khanna, Hargun K., LaSalle, Thomas J., Lavin-Parsons, Kendall M., Lilley, Brendan M., Lodenstein, Carl L., Manakongtreecheep, Kasidet, Margolin, Justin D., McKaig, Brenna N., Rojas-Lopez, Maricarmen, Russo, Brian C., Sharma, Nihaarika, Tantivit, Jessica, Thomas, Molly F., Gerszten, Robert E., Heimberg, Graham S., Hoover, Paul J., Lieb, David J., Lin, Brian, Ngo, Debby, Pelka, Karin, Reyes, Miguel, Smillie, Christopher S., Waghray, Avinash, Wood, Thomas E., Zajac, Amanda S., Jennings, Lori L., Grundberg, Ida, Bhattacharyya, Roby P., Parry, Blair Alden, Villani, Alexandra-Chloé, Sade-Feldman, Moshe, Hacohen, Nir, and Goldberg, Marcia B.

Published
2021
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50. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors.

Author

Fletcher, James, Griesbeck, Morgane, Butler, Andrew, Zheng, Shiwei, Lazo, Suzan, Jardine, Laura, Dixon, David, Stephenson, Emily, Nilsson, Emil, Grundberg, Ida, McDonald, David, Filby, Andrew, Li, Weibo, De Jager, Philip, Rozenblatt-Rosen, Orit, Lane, Andrew, Haniffa, Muzlifah, Regev, Aviv, Hacohen, Nir, Villani, Alexandra-Chloé, Satija, Rahul, Reynolds, Gary, Sarkizova, Siranush, and Shekhar, Karthik

Subjects
Adult, Antigen Presentation, Classification, Dendritic Cells, Female, Gene Expression Profiling, Humans, Lymphocyte Activation, Male, Monitoring, Immunologic, Monocytes, Neoplasms, Sequence Analysis, RNA, Single-Cell Analysis, T-Lymphocytes, Transcriptome, Young Adult
Abstract

Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C+ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease.

Published
2017

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