@article{4767a2755b3f46c8a75a22c5ea34d70a,
title = "Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy",
abstract = "Single-cell analyses of immune checkpoint blockade-associated colitis patient samples reveal enrichment of regulatory T cells in colitic lesions and nominate inflammatory pathways for potential therapeutic intervention.",
keywords = "CTLA-4, IFNγ, PD-1, TNFα, Trm, cancer, checkpoint blockade, cytotoxic T cells, immune-related adverse events, inflammatory cytokines, irAEs, tissue-resident memory T cells",
author = "Luoma, {Adrienne M.} and Shengbao Suo and Williams, {Hannah L.} and Tatyana Sharova and Keri Sullivan and Michael Manos and Peter Bowling and Hodi, {F. Stephen} and Osama Rahma and Sullivan, {Ryan J.} and Boland, {Genevieve M.} and Nowak, {Jonathan A.} and Dougan, {Stephanie K.} and Michael Dougan and Yuan, {Guo Cheng} and Wucherpfennig, {Kai W.}",
note = "Funding Information: This work was supported by a Team Award from the American Cancer Society ( MRAT-18-113-01 ), the Melanoma Research Alliance ( 597698 to K.W.W., S.K.D., M.D., G.-C.Y., and R.J.S.), NIH grants R01 CA238039 (to K.W.W.), P01 CA163222 (to K.W.W. and F.S.H.), and T32CA207021 (to A.M.L. and K.W.W.); National Institutes of Health Mentored Clinical Scientist Development Award 1K08DK114563-01 (to M.D.); and the American Gastroenterological Association Research Scholars Award (to M.D.). We would like to thank all of the patients who participated in this study and the nursing and surgical technicians from the MGH endoscopy unit who provided care for the patients and made safe biopsy collection feasible. We would further like to thank Md Aladdin Bhuiyan, Elisa Bello, Patrick Lenehan, and Max Heckler for providing specific technical assistance and Ruben Dries for helpful discussions. We thank Susannah Phillips, J. Harrison Carmichael, and Dennie Frederick for help with clinical sample collection. We thank the Center for Cancer Genome Discovery (DFCI) for sequencing of scRNA-seq libraries. Funding Information: This work was supported by a Team Award from the American Cancer Society (MRAT-18-113-01), the Melanoma Research Alliance (597698 to K.W.W. S.K.D. M.D. G.-C.Y. and R.J.S.), NIH grants R01 CA238039 (to K.W.W.), P01 CA163222 (to K.W.W. and F.S.H.), and T32CA207021 (to A.M.L. and K.W.W.); National Institutes of Health Mentored Clinical Scientist Development Award 1K08DK114563-01 (to M.D.); and the American Gastroenterological Association Research Scholars Award (to M.D.). We would like to thank all of the patients who participated in this study and the nursing and surgical technicians from the MGH endoscopy unit who provided care for the patients and made safe biopsy collection feasible. We would further like to thank Md Aladdin Bhuiyan, Elisa Bello, Patrick Lenehan, and Max Heckler for providing specific technical assistance and Ruben Dries for helpful discussions. We thank Susannah Phillips, J. Harrison Carmichael, and Dennie Frederick for help with clinical sample collection. We thank the Center for Cancer Genome Discovery (DFCI) for sequencing of scRNA-seq libraries. A.M.L. S.K.D. M.D. and K.W.W. designed the study. A.M.L. processed tissue biopsies, generated scRNA-seq gene expression libraries, and performed flow cytometry studies. S.S. and G.-C.Y. performed computational analyses. H.L.W. and J.A.N. performed immunofluorescence studies of tissue sections. M.D. supervised the clinical aspects of the study, enrolled patients, and performed endoscopic exams. T.S. K.S. M.M. and P.B. collected patient consent for the study and assisted with sample collection. F.S.H. O.R. R.J.S. and G.M.B. contributed to the clinical aspects of the study design. A.M.L. S.S. M.D. and K.W.W. wrote the paper with input from all authors. K.W.W. serves on the scientific advisory board of TCR2 Therapeutics, T-Scan Therapeutics, and Nextechinvest and receives sponsored research funding from Novartis. He is a scientific co-founder of Immunitas Therapeutics. M.D. receives research funding from Novartis and is on the Scientific Advisory Board for Neoleukin Therapeutics. S.K.D. receives research funding from Novartis, Bristol-Myers Squibb, and Eli Lilly. F.S.H. receives research funding from Bristol-Myers Squibb and Novartis; he also consults for Merck, EMD Serono, Novartis, Takeda, Genentech/Roche, Compass Therapeutics, Apricity, Aduro, Sanofi, Pionyr, 7 Hills Pharma, Verastem, Torque, Rheos Kairos, Psioxus Therapeutics, Amgen, and Pieris Pharmaceutical. O.R. receives research support from Merck and is a speaker for activities supported by educational grants from BMS and Merck. He is a consultant for Merck, Celgene, Five Prime, GSK, GFK, Bayer, Roche/Genentech, Puretech, Imvax, and Sobi. In addition, he has patent ?Methods of using pembrolizumab and trebananib? pending. J.A.N. has a provisional patent application for spatial quantification of immune cell infiltration in the tumor microenvironment. R.J.S. has received research funding from Merck and Amgen. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = aug,
day = "6",
doi = "10.1016/j.cell.2020.06.001",
language = "English",
volume = "182",
pages = "655--671.e22",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}