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3. Dietary protein modulates intestinal dendritic cells to establish mucosal homeostasis

Author

Moreira, Thais G., Cox, Laura M., Da Silva, Patrick, Mangani, Davide, De Oliveira, Marilia G., Escobar, Giulia, Lanser, Toby B., Murphy, Liam, Lobo, Eduardo.L.C., Milstein, Omer, Gauthier, Christian D., Clara Guimarāes, Ana, Schwerdtfeger, Luke, Ekwudo, Mellicient N., Wasén, Caroline, Liu, Shirong, Menezes, Gustavo B., Ferreira, Enio, Gabriely, Galina, Anderson, Ana C., Faria, Ana Maria C., Rezende, Rafael M., and Weiner, Howard L.

Published
2024
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5. Retraction: TIGIT predominantly regulates the immune response via regulatory T cells

Author

Kurtulus, Sema, Sakuishi, Kaori, Ngiow, Shin-Foong, Joller, Nicole, Tan, Dewar J., Teng, Michele W.L., Smyth, Mark J., Kuchroo, Vijay K., and Anderson, Ana C.

Abstract

Original citation: J Clin Invest. 2015;125(11):4053-4062. https://doi.org/10.1172/JCI81187. Citation for this retraction: J Clin Invest. 2024;134(13):e183278. https://doi.org/10.1172/JCI183278. QIMR Berghofer Medical Research Institute recently notified the JCI of concerns regarding Figure 4B [...]

Published
2024

8. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling

Author

Cadinu, Paolo, Sivanathan, Kisha N., Misra, Aditya, Xu, Rosalind J., Mangani, Davide, Yang, Evan, Rone, Joseph M., Tooley, Katherine, Kye, Yoon-Chul, Bod, Lloyd, Geistlinger, Ludwig, Lee, Tyrone, Mertens, Randall T., Ono, Noriaki, Wang, Gang, Sanmarco, Liliana, Quintana, Francisco J., Anderson, Ana C., Kuchroo, Vijay K., Moffitt, Jeffrey R., and Nowarski, Roni

Published
2024
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10. TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory

Author

Ausejo-Mauleon, Iker, Labiano, Sara, de la Nava, Daniel, Laspidea, Virginia, Zalacain, Marta, Marrodán, Lucía, García-Moure, Marc, González-Huarriz, Marisol, Hervás-Corpión, Irati, Dhandapani, Laasya, Vicent, Silvestre, Collantes, Maria, Peñuelas, Iván, Becher, Oren J., Filbin, Mariella G., Jiang, Li, Labelle, Jenna, de Biagi-Junior, Carlos A.O., Nazarian, Javad, Laternser, Sandra, Phoenix, Timothy N., van der Lugt, Jasper, Kranendonk, Mariette, Hoogendijk, Raoull, Mueller, Sabine, De Andrea, Carlos, Anderson, Ana C., Guruceaga, Elizabeth, Koschmann, Carl, Yadav, Viveka Nand, Gállego Pérez-Larraya, Jaime, Patiño-García, Ana, Pastor, Fernando, and Alonso, Marta M.

Published
2023
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12. Author Correction: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion

Author

Huang, Yu-Hwa, Zhu, Chen, Kondo, Yasuyuki, Anderson, Ana C., Gandhi, Amit, Russell, Andrew, Dougan, Stephanie K., Petersen, Britt-Sabina, Melum, Espen, Pertel, Thomas, Clayton, Kiera L., Raab, Monika, Chen, Qiang, Beauchemin, Nicole, Yazaki, Paul J., Pyzik, Michal, Ostrowski, Mario A., Glickman, Jonathan N., Rudd, Christopher E., Ploegh, Hidde L., Franke, Andre, Petsko, Gregory A., Kuchroo, Vijay K., and Blumberg, Richard S.

Published
2024
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14. Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling

Author

Pawlak, Mathias, DeTomaso, David, Schnell, Alexandra, Meyer zu Horste, Gerd, Lee, Youjin, Nyman, Jackson, Dionne, Danielle, Regan, Brianna M.L., Singh, Vasundhara, Delorey, Toni, Schramm, Markus A., Wang, Chao, Wallrapp, Antonia, Burkett, Patrick R., Riesenfeld, Samantha J., Anderson, Ana C., Regev, Aviv, Xavier, Ramnik J., Yosef, Nir, and Kuchroo, Vijay K.

Published
2022
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16. Tumors recycle glucocorticoids to drive Treg-mediated immunosuppression

Author

Swatler, Julian, Ju, Young-Jun, Anderson, Ana C., and Lugli, Enrico

Subjects
Drug therapy, Physiological aspects, Development and progression, Research, Health aspects, Cancer research, Suppressor cells -- Physiological aspects -- Health aspects, Immunosuppression -- Health aspects, Tumors -- Development and progression -- Drug therapy, Immunotherapy -- Research, Glucocorticoids -- Physiological aspects -- Health aspects, Oncology, Experimental, Corticosteroids -- Physiological aspects -- Health aspects, Cancer -- Research
Abstract

Glucocorticoids mediate immunosuppression Immunosuppression is a prominent feature of cancer development, restraining antitumor effector T cell responses and limiting efficacy of therapeutic interventions. Immunosuppression can be mediated by multiple mechanisms, [...], Suppression of antitumor immunity is a prominent feature of the tumor microenvironment. In this issue of the JCI, Taves, Otsuka, and authors show that glucocorticoids (GCs), which are potent immunosuppressive hormones mainly produced by the adrenals, can be reconverted from their inactive form to active metabolites via the 11[beta]-hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1) enzyme expressed by murine tumor cell lines. In the tumor microenvironment, GCs acted on CD[4.sup.+] regulatory T cells to enhance their immunosuppressive function and promote tumor growth. The findings suggest that targeting GC recycling as a strategy for modulating tumor immunosuppression has the potential to improve therapeutic efficacy of immune checkpoint blockade.

Published
2023
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17. Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps

Author

Chen, Bob, Scurrah, Cherie’ R., McKinley, Eliot T., Simmons, Alan J., Ramirez-Solano, Marisol A., Zhu, Xiangzhu, Markham, Nicholas O., Heiser, Cody N., Vega, Paige N., Rolong, Andrea, Kim, Hyeyon, Sheng, Quanhu, Drewes, Julia L., Zhou, Yuan, Southard-Smith, Austin N., Xu, Yanwen, Ro, James, Jones, Angela L., Revetta, Frank, Berry, Lynne D., Niitsu, Hiroaki, Islam, Mirazul, Pelka, Karin, Hofree, Matan, Chen, Jonathan H., Sarkizova, Siranush, Ng, Kimmie, Giannakis, Marios, Boland, Genevieve M., Aguirre, Andrew J., Anderson, Ana C., Rozenblatt-Rosen, Orit, Regev, Aviv, Hacohen, Nir, Kawasaki, Kenta, Sato, Toshiro, Goettel, Jeremy A., Grady, William M., Zheng, Wei, Washington, M. Kay, Cai, Qiuyin, Sears, Cynthia L., Goldenring, James R., Franklin, Jeffrey L., Su, Timothy, Huh, Won Jae, Vandekar, Simon, Roland, Joseph T., Liu, Qi, Coffey, Robert J., Shrubsole, Martha J., and Lau, Ken S.

Published
2021
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18. Spatially organized multicellular immune hubs in human colorectal cancer

Author

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

Published
2021
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19. Male sex chromosomal complement exacerbates the pathogenicity of Th17 cells in a chronic model of central nervous system autoimmunity

Author

Doss, Prenitha Mercy Ignatius Arokia, Umair, Muhammad, Baillargeon, Joanie, Fazazi, Reda, Fudge, Neva, Akbar, Irshad, Yeola, Asmita Pradeep, Williams, John B., Leclercq, Mickael, Joly-Beauparlant, Charles, Beauchemin, Philippe, Ruda, Gian Filipo, Alpaugh, Melanie, Anderson, Ana C., Brennan, Paul E., Droit, Arnaud, Lassmann, Hans, Moore, Craig S., and Rangachari, Manu

Published
2021
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21. An IL-27-Driven Transcriptional Network Identifies Regulators of IL-10 Expression across T Helper Cell Subsets

Author

Zhang, Huiyuan, Madi, Asaf, Yosef, Nir, Chihara, Norio, Awasthi, Amit, Pot, Caroline, Lambden, Conner, Srivastava, Amitabh, Burkett, Patrick R., Nyman, Jackson, Christian, Elena, Etminan, Yasaman, Lee, Annika, Stroh, Helene, Xia, Junrong, Karwacz, Katarzyna, Thakore, Pratiksha I., Acharya, Nandini, Schnell, Alexandra, Wang, Chao, Apetoh, Lionel, Rozenblatt-Rosen, Orit, Anderson, Ana C., Regev, Aviv, and Kuchroo, Vijay K.

Published
2020
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22. Endogenous Glucocorticoid Signaling Regulates CD8+ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment

Author

Acharya, Nandini, Madi, Asaf, Zhang, Huiyuan, Klapholz, Max, Escobar, Giulia, Dulberg, Shai, Christian, Elena, Ferreira, Michelle, Dixon, Karen O., Fell, Geoffrey, Tooley, Katherine, Mangani, Davide, Xia, Junrong, Singer, Meromit, Bosenberg, Marcus, Neuberg, Donna, Rozenblatt-Rosen, Orit, Regev, Aviv, Kuchroo, Vijay K., and Anderson, Ana C.

Published
2020
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24. Consensus nomenclature for CD8+ T cell phenotypes in cancer

Author

Apetoh, Lionel, Smyth, Mark J, Drake, Charles G, Abastado, Jean-Pierre, Apte, Ron N, Ayyoub, Maha, Blay, Jean-Yves, Bonneville, Marc, Butterfield, Lisa H, Caignard, Anne, Castelli, Chiara, Cavallo, Federica, Celis, Esteban, Chen, Lieping, Colombo, Mario P, Comin-Anduix, Begoña, Coukos, Georges, Dhodapkar, Madhav V, Dranoff, Glenn, Frazer, Ian H, Fridman, Wolf-Hervé, Gabrilovich, Dmitry I, Gilboa, Eli, Gnjatic, Sacha, Jäger, Dirk, Kalinski, Pawel, Kaufman, Howard L, Kiessling, Rolf, Kirkwood, John, Knuth, Alexander, Liblau, Roland, Lotze, Michael T, Lugli, Enrico, Marincola, Francesco, Melero, Ignacio, Melief, Cornelis J, Mempel, Thorsten R, Mittendorf, Elizabeth A, Odun, Kunle, Overwijk, Willem W, Palucka, Anna Karolina, Parmiani, Giorgio, Ribas, Antoni, Romero, Pedro, Schreiber, Robert D, Schuler, Gerold, Srivastava, Pramod K, Tartour, Eric, Valmori, Danila, van der Burg, Sjoerd H, van der Bruggen, Pierre, van den Eynde, Benoît J, Wang, Ena, Zou, Weiping, Whiteside, Theresa L, Speiser, Daniel E, Pardoll, Drew M, Restifo, Nicholas P, and Anderson, Ana C

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, 2.1 Biological and endogenous factors, Aetiology, anergy, anticancer immunity, CD8(+) T cells, cytotoxicity, exhaustion, effector, IFN gamma, senescence, stemness, CD8+ T cells, IFNγ, Oncology and carcinogenesis
Abstract

Whereas preclinical investigations and clinical studies have established that CD8+ T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8+ T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8+ T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8+ T cell immunity, leading to the emergence of dysfunctional CD8+ T cells. The existence of different types of CD8+ T cells in cancer calls for a more precise definition of the CD8+ T cell immune phenotypes in cancer and the abandonment of the generic terms "pro-tumor" and "antitumor." Based on recent studies investigating the functions of CD8+ T cells in cancer, we here propose some guidelines to precisely define the functional states of CD8+ T cells in cancer.

Published
2015

30. Tim-3 mediates T cell trogocytosis to limit antitumor immunity

Author

Pagliano, Ornella, Morrison, Robert M., Chauvin, Joe-Marc, Banerjee, Hridesh, Davar, Diwakar, Ding, Quanquan, Tanegashima, Tokiyoshi, Gao, Wentao, Chakka, Saranya R., DeBlasio, Richelle, Lowin, Ava, Kara, Kevin, Ka, Mignane, Zidi, Bochra, Amin, Rada, Raphael, Itay, Zhang, Shuowen, Watkins, Simon C., Sander, Cindy, Kirkwood, John M., Bosenberg, Marcus, Anderson, Ana C., Kuchroo, Vijay K., Kane, Lawrence P., Korman, Alan J., Rajpal, Arvind, West, Sean M., Han, Minhua, Bee, Christine, Deng, Xiaodi, Schebye, Xiao Min, Strop, Pavel, and Zarour, Hassane M.

Subjects
Physiological aspects, Development and progression, Research, Health aspects, Immunity (Physiology) -- Research, Cell interactions -- Research, Cancer research, Melanoma -- Development and progression, Membrane proteins -- Health aspects -- Physiological aspects, T cells -- Health aspects -- Physiological aspects, Oncology, Experimental, Immunity -- Research, Cell interaction -- Research, Cancer -- Research
Abstract

Introduction During chronic viral infection and cancer, tumor antigen-specific (TA-specific) [CD8.sup.+] T cells become dysfunctional and upregulate multiple inhibitory receptors, including programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) and [...], T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1-positive ([PD-1.sup.+]) [Tim-3.sup.+][CD8.sup.+] tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis. Tim-3 blockade acted on [Tim-3.sup.+] APCs in a PS-dependent fashion to disrupt the trogocytosis of activated tumor antigen-specific [CD8.sup.+] T cells and [PD-1.sup.+][Tim-3.sup.+] [CD8.sup.+] TILs isolated from patients with melanoma. Tim-3 and PD-1 blockades cooperated to disrupt trogocytosis of [CD8.sup.+] TILs in 2 melanoma mouse models, decreasing tumor burden and prolonging survival. Deleting Tim-3 in dendritic cells but not in [CD8.sup.+] T cells impeded the trogocytosis of [CD8.sup.+] TILs in vivo. Trogocytosed [CD8.sup.+] T cells presented tumor peptide-major histocompatibility complexes and became the target of fratricide T cell killing, which was reversed by Tim-3 blockade. Our findings have uncovered a mechanism Tim-3 uses to limit antitumor immunity.

Published
2022
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32. Induction and transcriptional regulation of the co-inhibitory gene module in T cells

Author

Chihara, Norio, Madi, Asaf, Kondo, Takaaki, Zhang, Huiyuan, Acharya, Nandini, Singer, Meromit, Nyman, Jackson, Marjanovic, Nemanja D., Kowalczyk, Monika S., Wang, Chao, Kurtulus, Sema, Law, Travis, Etminan, Yasaman, Nevin, James, Buckley, Christopher D., Burkett, Patrick R., Buenrostro, Jason D., Rozenblatt-Rosen, Orit, Anderson, Ana C., Regev, Aviv, and Kuchroo, Vijay K.

Published
2018
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36. Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function

Author

Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research at MIT, Tang, Ruihan, Acharya, Nandini, Subramanian, Ayshwarya, Purohit, Vinee, Tabaka, Marcin, Hou, Yu, He, Danyang, Dixon, Karen O, Lambden, Connor, Xia, Junrong, Rozenblatt-Rosen, Orit, Sobel, Raymond A, Wang, Chao, Regev, Aviv, Anderson, Ana C, Kuchroo, Vijay K, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research at MIT, Tang, Ruihan, Acharya, Nandini, Subramanian, Ayshwarya, Purohit, Vinee, Tabaka, Marcin, Hou, Yu, He, Danyang, Dixon, Karen O, Lambden, Connor, Xia, Junrong, Rozenblatt-Rosen, Orit, Sobel, Raymond A, Wang, Chao, Regev, Aviv, Anderson, Ana C, and Kuchroo, Vijay K

Abstract

Dendritic cells (DCs) sense environmental cues and adopt either an immune-stimulatory or regulatory phenotype, thereby fine-tuning immune responses. Identifying endogenous regulators that determine DC function can thus inform the development of therapeutic strategies for modulating the immune response in different disease contexts. Tim-3 plays an important role in regulating immune responses by inhibiting the activation status and the T cell priming ability of DC in the setting of cancer. Bat3 is an adaptor protein that binds to the tail of Tim-3; therefore, we studied its role in regulating the functional status of DCs. In murine models of autoimmunity (experimental autoimmune encephalomyelitis) and cancer (MC38-OVA–implanted tumor), lack of Bat3 expression in DCs alters the T cell compartment—it decreases TH1, TH17 and cytotoxic effector cells, increases regulatory T cells, and exhausted CD8+tumor-infiltrating lymphocytes, resulting in the attenuation of autoimmunity and acceleration of tumor growth. We found that Bat3 expression levels were differentially regulated by activating versus inhibitory stimuli in DCs, indicating a role for Bat3 in the functional calibration of DC phenotypes. Mechanistically, loss of Bat3 in DCs led to hyperactive unfolded protein response and redirected acetyl–coenzyme A to increase cell intrinsic steroidogenesis. The enhanced steroidogenesis in Bat3-deficient DC suppressed T cell response in a paracrine manner. Our findings identified Bat3 as an endogenous regulator of DC function, which has implications for DC-based immunotherapies.

Published
2023

37. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling

Author

Cadinu, Paolo, primary, Sivanathan, Kisha N, additional, Misra, Aditya, additional, Xu, Rosalind J, additional, Mangani, Davide, additional, Yang, Evan, additional, Rone, Joseph M, additional, Tooley, Katerine, additional, Kye, Yoon-Chul, additional, Bod, Lloyd, additional, Geistlinger, Ludwig, additional, Lee, Tyrone, additional, Ono, Noriaki, additional, Wang, Gang, additional, Sanmarco, Liliana, additional, Quintana, Francisco J, additional, Anderson, Ana C, additional, Kuchroo, Vijay K, additional, Moffitt, Jeffrey R, additional, and Nowarski, Roni, additional

Published
2023
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43. Supplementary Data from Targeting CD39 in Cancer Reveals an Extracellular ATP- and Inflammasome-Driven Tumor Immunity

Author

Li, Xian-Yang, primary, Moesta, Achim K., primary, Xiao, Christos, primary, Nakamura, Kyohei, primary, Casey, Mika, primary, Zhang, Haiyan, primary, Madore, Jason, primary, Lepletier, Ailin, primary, Aguilera, Amelia Roman, primary, Sundarrajan, Ashmitha, primary, Jacoberger-Foissac, Celia, primary, Wong, Clifford, primary, dela Cruz, Tracy, primary, Welch, Megan, primary, Lerner, Alana G., primary, Spatola, Bradley N., primary, Soros, Vanessa B., primary, Corbin, John, primary, Anderson, Ana C., primary, Effern, Maike, primary, Hölzel, Michael, primary, Robson, Simon C., primary, Johnston, Rebecca L., primary, Waddell, Nicola, primary, Smith, Corey, primary, Bald, Tobias, primary, Geetha, Nishamol, primary, Beers, Courtney, primary, Teng, Michele W. L., primary, and Smyth, Mark J., primary

Published
2023
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45. Data from Targeting CD39 in Cancer Reveals an Extracellular ATP- and Inflammasome-Driven Tumor Immunity

Author

Li, Xian-Yang, primary, Moesta, Achim K., primary, Xiao, Christos, primary, Nakamura, Kyohei, primary, Casey, Mika, primary, Zhang, Haiyan, primary, Madore, Jason, primary, Lepletier, Ailin, primary, Aguilera, Amelia Roman, primary, Sundarrajan, Ashmitha, primary, Jacoberger-Foissac, Celia, primary, Wong, Clifford, primary, dela Cruz, Tracy, primary, Welch, Megan, primary, Lerner, Alana G., primary, Spatola, Bradley N., primary, Soros, Vanessa B., primary, Corbin, John, primary, Anderson, Ana C., primary, Effern, Maike, primary, Hölzel, Michael, primary, Robson, Simon C., primary, Johnston, Rebecca L., primary, Waddell, Nicola, primary, Smith, Corey, primary, Bald, Tobias, primary, Geetha, Nishamol, primary, Beers, Courtney, primary, Teng, Michele W. L., primary, and Smyth, Mark J., primary

Published
2023
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