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1. Immune responses in checkpoint myocarditis across heart, blood and tumour

Author

Blum, Steven M., Zlotoff, Daniel A., Smith, Neal P., Kernin, Isabela J., Ramesh, Swetha, Zubiri, Leyre, Caplin, Joshua, Samanta, Nandini, Martin, Sidney, Wang, Mike, Tirard, Alice, Song, Yuhui, Xu, Katherine H., Barth, Jaimie, Sen, Pritha, Slowikowski, Kamil, Tantivit, Jessica, Manakongtreecheep, Kasidet, Arnold, Benjamin Y., Nasrallah, Mazen, Pinto, Christopher J., McLoughlin, Daniel, Jackson, Monica, Chan, PuiYee, Lawless, Aleigha, Michaud, William A., Sharova, Tatyana, Nieman, Linda T., Gainor, Justin F., Wu, Catherine J., Juric, Dejan, Mino-Kenudson, Mari, Oliveira, Giacomo, Sullivan, Ryan J., Boland, Genevieve M., Stone, James R., Thomas, Molly F., Neilan, Tomas G., Reynolds, Kerry L., and Villani, Alexandra-Chloé

Published
2024
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2. A γδ T cell–IL-3 axis controls allergic responses through sensory neurons

Author

Flayer, Cameron H., Kernin, Isabela J., Matatia, Peri R., Zeng, Xiangsunze, Yarmolinsky, David A., Han, Cai, Naik, Parth R., Buttaci, Dean R., Aderhold, Pamela A., Camire, Ryan B., Zhu, Xueping, Tirard, Alice J., McGuire, John T., Smith, Neal P., McKimmie, Clive S., McAlpine, Cameron S., Swirski, Filip K., Woolf, Clifford J., Villani, Alexandra-Chloe, and Sokol, Caroline L.

Published
2024
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3. 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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4. SARS-CoV-2 infection elucidates features of pregnancy-specific immunity

Author

Oh, Dong Sun, Kim, Eunha, Normand, Rachelly, Lu, Guangqing, Shook, Lydia L., Lyall, Amanda, Jasset, Olyvia, Demidkin, Stepan, Gilbert, Emily, Kim, Joon, Akinwunmi, Babatunde, Tantivit, Jessica, Tirard, Alice, Arnold, Benjamin Y., Slowikowski, Kamil, Goldberg, Marcia B., Filbin, Michael R., Hacohen, Nir, Nguyen, Long H., Chan, Andrew T., Yu, Xu G., Li, Jonathan Z., Yonker, Lael, Fasano, Alessio, Perlis, Roy H., Pasternak, Ofer, Gray, Kathryn J., Choi, Gloria B., Drew, David A., Sen, Pritha, Villani, Alexandra-Chloé, Edlow, Andrea G., and Huh, Jun R.

Published
2024
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6. Abstract 11983: Associations Between Circulating Proteins and Intracardiac Immune Populations in Immune Checkpoint Inhibitor-Associated Myocarditis

Author

Zlotoff, Daniel, Blum, Steven, Ramesh, Swetha, Kernin, Isabela, Smith, Neal, Sen, Pritha, Zubiri, Leyre, Tirard, Alice, Nasrallah, Mazen, Tantivit, Jessica, Manakongtreecheep, Kasidet, Arnold, Benjamin, Chan, PuiYee, Barth, Jaimie, Juric, Dejan, Sullivan, Ryan, Boland, Genevieve, Mino-Kenudson, Mari, Stone, James R, Thomas, Molly F, Caplin, Joshua, Reynolds, Kerry, Neilan, Tomas G, and Villani, Alexandra-Chloe

Published
2022
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7. 1255 Single cell dissection of human checkpoint inhibitor hepatitis reveals insights into liver immune tolerance

Author

Thomas, Molly, primary, Chan, Tos, additional, Smith, Neal, additional, Sonthalia, Shreyash, additional, Sherman, Marc, additional, Ramesh, Swetha, additional, Tirard, Alice, additional, McGuire, John, additional, Nasrallah, Mazen, additional, Manakongtreecheep, Kasidet, additional, Tantivit, Jessica, additional, Zubiri, Leyre, additional, Juric, Dejan, additional, Sullivan, Ryan, additional, Hacohen, Nir, additional, Boland, Genevieve M, additional, Lauer, Georg, additional, Reynolds, Kerry, additional, and Villani, Alexandra-Chloe, additional

Published
2023
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8. 1252 Immune checkpoint inhibitor-induced diabetes mellitus comprises multiple clinical endotypes with distinct immunologic features

Author

Rengarajan, Michelle, primary, Esteves, Karina Ruiz, additional, Fernandez, Sergio Aguilar, additional, Shank, Kaitlyn, additional, Deutsch, Aaron, additional, Zubiri, Leyre, additional, Colling, Caitlin, additional, Tran, Hoang, additional, Gunturi, Alekhya, additional, McGuire, John, additional, Tirard, Alice, additional, Arnold, Benjamin, additional, Samanta, Nandini, additional, Martin, Sidney, additional, Perlman, Katherine, additional, Ouyang, Tianqi, additional, Gusev, Alexander, additional, Juric, Dejan, additional, Boland, Genevieve M, additional, Sise, Meghan, additional, Reynolds, Kerry, additional, and Villani, Alexandra-Chloe, additional

Published
2023
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9. Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor

Author

Blum, Steven M., primary, Zlotoff, Daniel A., additional, Smith, Neal P., additional, Kernin, Isabela J., additional, Ramesh, Swetha, additional, Zubiri, Leyre, additional, Caplin, Joshua, additional, Tirard, Alice, additional, Sen, Prith, additional, Song, Yuhui, additional, Barth, Jaimie L., additional, Slowikowski, Kamil, additional, Nasrallah, Mazen, additional, Tantivit, Jessica, additional, Manakongtreecheep, Kasidet, additional, Arnold, Benjamin Y., additional, McGuire, John, additional, Pinto, Christopher J., additional, McLoughlin, Daniel, additional, Jackson, Monica, additional, Chan, PuiYee, additional, Lawless, Aleigha, additional, Sharova, Tatyana, additional, Nieman, Linda T., additional, Gainor, Justin F., additional, Juric, Dejan, additional, Mino-Kenudsen, Mari, additional, Sullivan, Ryan J., additional, Boland, Genevieve M., additional, Stone, James R., additional, Thomas, Molly F., additional, Neilan, Tomas G., additional, Reynolds, Kerry L., additional, and Villani, Alexandra-Chloe, additional

Published
2023
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10. 1254 Distinguishing T-cell responses in paired heart and tumor samples from patients with immune checkpoint-related myocarditis

Author

Blum, Steven, primary, Smith, Neal, additional, Zlotoff, Daniel, additional, Barth, Jaimie, additional, Ramesh, Swetha, additional, Kernin, Isabela, additional, Zubiri, Leyre, additional, McGuire, John, additional, Tirard, Alice, additional, Juric, Dejan, additional, Sullivan, Ryan, additional, Boland, Genevieve, additional, Mino-Kenudson, Mari, additional, Stone, James, additional, Thomas, Molly, additional, Reynolds, Kerry, additional, Neilan, Thomas, additional, and Villani, Chloe, additional

Published
2022
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11. 1242 Altered interactions between circulating and tissue-resident CD8 T cells with the colonic mucosa define checkpoint inhibitor colitis

Author

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

Published
2022
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12. 441 Checkpoint inhibitor-associated inflammatory arthritis is comprised of multiple clinical endotypes characterized by distinct transcriptional programs

Author

Reynolds, Gary, primary, Nasrallah, Mazen, additional, Smith, Neal, additional, Thomas, Molly, additional, Zubiri, Leyre, additional, Tirard, Alice, additional, McGuire, John, additional, Manakongtreecheep, Kasidet, additional, Tantivit, Jessica, additional, Blum, Steven, additional, Zlotoff, Daniel, additional, Chan, Elaina PuiYee, additional, Juric, Dejan, additional, Sullivan, Ryan, additional, Boland, Genevieve, additional, Luster, Andrew, additional, Schoenfeld, Sara, additional, Kohler, Minna, additional, Reynolds, Kerry, additional, and Villani, Chloe, additional

Published
2022
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13. 1257 Single cell immunologic dissection of checkpoint inhibitor hepatitis and autoimmune hepatitis reveals insights into immune tolerance in the human liver

Author

Thomas, Molly, primary, Chan, Tos, additional, Smith, Neal, additional, Sherman, Marc, additional, Ramesh, Swetha, additional, Tirard, Alice, additional, McGuire, John, additional, Nasrallah, Mazen, additional, Manakongtreecheep, Kasidet, additional, Tantivit, Jessica, additional, Zubiri, Leyre, additional, Juric, Dejan, additional, Sullivan, Ryan, additional, Boland, Genevieve, additional, Lauer, Georg, additional, Hacohen, Nir, additional, Reynolds, Kerry, additional, and Villani, Chloe, additional

Published
2022
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14. Single-cell profiling of human heart and blood in immune checkpoint inhibitor-associated myocarditis.

Author

Blum, Steven Michael, primary, Zlotoff, Daniel A., additional, Smith, Neal, additional, Ramesh, Swetha, additional, Kernin, Isabela, additional, Sen, Pritha, additional, Zubiri, Leyre, additional, Tirard, Alice, additional, Nasrallah, Mazen, additional, Tantivit, Jessica, additional, Barth, Jaimie Lynn, additional, Juric, Dejan, additional, Sullivan, Ryan J., additional, Boland, Genevieve Marie, additional, Mino-Kenudson, Mari, additional, Stone, James, additional, Thomas, Molly, additional, Reynolds, Kerry Lynn, additional, Neilan, Tomas G., additional, and Villani, Alexandra-Chloé, additional

Published
2022
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17. Altered interactions between circulating and tissue-resident CD8 T cells with the colonic mucosa define colitis associated with immune checkpoint inhibitors

Author

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

Published
2021
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18. Single-Cell Multiomics Analysis Reveals Potential Drivers of Response to the Anti-TIM3 Inhibitor Sabatolimab Combined with Azacitidine in MDS and CMML

Author

Dey, Aonkon, Narayan, Rupa, Smith, Neal, Tirard, Alice, Arnold, Benjamin, McGuire, John, Chan, Thomas, Lombardi Story, Jennifer, Casson, Timothy, Behnan, Tanya Toni, Fathi, Amir T., Hobbs, Gabriela S., Hock, Hanno, Amrein, Philip C., Reeves, Patrick, Graubert, Timothy Aaron, Brunner, Andrew M., and Villani, Alexandra-Chloé

Published
2023
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19. SARS-CoV-2 infection elucidates unique features of pregnancy-specific immunity.

Author

Oh DS, Kim E, Lu G, Normand R, Shook LL, Lyall A, Jasset O, Demidkin S, Gilbert E, Kim J, Akinwunmi B, Tantivit J, Tirard A, Arnold BY, Slowikowski K, Goldberg MB, Filbin MR, Hacohen N, Nguyen LH, Chan AT, Yu XG, Li JZ, Yonker L, Fasano A, Perlis RH, Pasternak O, Gray KJ, Choi GB, Drew DA, Sen P, Villani AC, Edlow AG, and Huh JR

Abstract

Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understanding of how pregnancy shapes immune responses. To gain insight into the role of pregnancy in modulating immune responses at steady state and upon perturbation, we collected peripheral blood mononuclear cells (PBMC), plasma, and stool from 226 women, including 152 pregnant individuals (n = 96 with SARS-CoV-2 infection and n = 56 healthy controls) and 74 non-pregnant women (n = 55 with SARS-CoV-2 and n = 19 healthy controls). We found that SARS-CoV-2 infection was associated with altered T cell responses in pregnant compared to non-pregnant women. Differences included a lower percentage of memory T cells, a distinct clonal expansion of CD4-expressing CD8 + T cells, and the enhanced expression of T cell exhaustion markers, such as programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain-3 (Tim-3), in pregnant women. We identified additional evidence of immune dysfunction in severely and critically ill pregnant women, including a lack of expected elevation in regulatory T cell (Treg) levels, diminished interferon responses, and profound suppression of monocyte function. Consistent with earlier data, we found maternal obesity was also associated with altered immune responses to SARS-CoV-2 infection, including enhanced production of inflammatory cytokines by T cells. Certain gut bacterial species were altered in pregnancy and upon SARS-CoV-2 infection in pregnant individuals compared to non-pregnant women. Shifts in cytokine and chemokine levels were also identified in the sera of pregnant individuals, most notably a robust increase of interleukin-27 (IL-27), a cytokine known to drive T cell exhaustion, in the pregnant uninfected control group compared to all non-pregnant groups. IL-27 levels were also significantly higher in uninfected pregnant controls compared to pregnant SARS-CoV-2-infected individuals. Using two different preclinical mouse models of inflammation-induced fetal demise and respiratory influenza viral infection, we found that enhanced IL-27 protects developing fetuses from maternal inflammation but renders adult female mice vulnerable to viral infection. These combined findings from human and murine studies reveal nuanced pregnancy-associated immune responses, suggesting mechanisms underlying the increased susceptibility of pregnant individuals to viral respiratory infections.

Published
2024
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20. Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor.

Author

Blum SM, Zlotoff DA, Smith NP, Kernin IJ, Ramesh S, Zubiri L, Caplin J, Samanta N, Martin SC, Tirard A, Sen P, Song Y, Barth J, Slowikowski K, Nasrallah M, Tantivit J, Manakongtreecheep K, Arnold BY, McGuire J, Pinto CJ, McLoughlin D, Jackson M, Chan P, Lawless A, Sharova T, Nieman LT, Gainor JF, Juric D, Mino-Kenudsen M, Sullivan RJ, Boland GM, Stone JR, Thomas MF, Neilan TG, Reynolds KL, and Villani AC

Abstract

Immune checkpoint inhibitors (ICIs) are widely used anti-cancer therapies that can cause morbid and potentially fatal immune-related adverse events (irAEs). ICI-related myocarditis (irMyocarditis) is uncommon but has the highest mortality of any irAE. The pathogenesis of irMyocarditis and its relationship to anti-tumor immunity remain poorly understood. We sought to define immune responses in heart, tumor, and blood during irMyocarditis and identify biomarkers of clinical severity by leveraging single-cell (sc)RNA-seq coupled with T cell receptor (TCR) sequencing, microscopy, and proteomics analysis of 28 irMyocarditis patients and 23 controls. Our analysis of 284,360 cells from heart and blood specimens identified cytotoxic T cells, inflammatory macrophages, conventional dendritic cells (cDCs), and fibroblasts enriched in irMyocarditis heart tissue. Additionally, potentially targetable, pro-inflammatory transcriptional programs were upregulated across multiple cell types. TCR clones enriched in heart and paired tumor tissue were largely non-overlapping, suggesting distinct T cell responses within these tissues. We also identify the presence of cardiac-expanded TCRs in a circulating, cycling CD8 T cell population as a novel peripheral biomarker of fatality. Collectively, these findings highlight critical biology driving irMyocarditis and putative biomarkers for therapeutic intervention., Competing Interests: Conflict of Interest S.M.B has been a paid consultant to Two River Consulting and Third Rock Ventures. He has equity positions in Kronos Bio, 76Bio, and Allogene Therapeutics. D.A.Z. has been a paid consultant to Bristol Myers Squibb, Freeline Therapeutics, and Intrinsic Imaging. L.Z. has received consulting fees from Bristol Myers Squibb and Merck. R.J.S has been a paid consultant to Bristol Myers Squibb, Merck, Pfizer, Marengo Therapeutics, Novartis, Eisai, Iovance, OncoSec, and AstraZeneca and has received research funding from Merck. T.G.N has been a paid consultant to Bristol Myers Squibb, Genentech, CRC Oncology, Roche, Sanofi and Parexel Imaging Pharmaceuticals and has received grant funding from Astra Zeneca and Bristol Myers Squibb related to the cardiac effects of immune checkpoint inhibitors. K.L.R has served as an advisory board to SAGA Diagnostics and received speaker’s fees from CMEOutfitters and Medscape as well as research funding from Bristol Myers Squibb. A.C.V. has been a paid consultant to Bristol Myers Squibb.

Published
2023
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