Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy

Adrienne M Luoma ¹, Shengbao Suo ², Hannah L Williams ³, Tatyana Sharova ⁴, Keri Sullivan ⁵, Michael Manos ⁶, Peter Bowling ⁶, F Stephen Hodi ⁶, Osama Rahma ⁷, Ryan J Sullivan ⁸, Genevieve M Boland ⁴, Jonathan A Nowak ⁹, Stephanie K Dougan ¹, Michael Dougan ¹⁰, Guo-Cheng Yuan ², Kai W Wucherpfennig ¹¹

Affiliations

¹ Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
² Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute Boston, MA 02215, USA.
⁴ Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
⁵ Division of Gastroenterology and Department of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute Boston, MA 02215, USA; Center for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
⁷ Department of Medical Oncology, Dana-Farber Cancer Institute Boston, MA 02215, USA; Brigham and Women's Hospital and Dana-Farber/Harvard Cancer Center, Boston, MA, USA.
⁸ Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁹ Department of Pathology, Brigham & Women's Hospital, Boston, MA 02115, USA.
¹⁰ Division of Gastroenterology and Department of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA. Electronic address: mldougan@partners.org.
¹¹ Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: kai_wucherpfennig@dfci.harvard.edu.

PMID: 32603654
62 References
58 citations

Abstract

Checkpoint blockade with antibodies specific for the PD-1 and CTLA-4 inhibitory receptors can induce durable responses in a wide range of human cancers. However, the immunological mechanisms responsible for severe inflammatory side effects remain poorly understood. Here we report a comprehensive single-cell analysis of immune cell populations in colitis, a common and severe side effect of checkpoint blockade. We observed a striking accumulation of CD8 T cells with highly cytotoxic and proliferative states and no evidence of regulatory T cell depletion. T cell receptor (TCR) sequence analysis demonstrated that a substantial fraction of colitis-associated CD8 T cells originated from tissue-resident populations, explaining the frequently early onset of colitis symptoms following treatment initiation. Our analysis also identified cytokines, chemokines, and surface receptors that could serve as therapeutic targets for colitis and potentially other inflammatory side effects of checkpoint blockade.

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.

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References
Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Dvir Aran, Agnieszka P Looney, +9 authors, Mallar Bhattacharya. less Nat Immunol, 2019 Jan 16; 20(2). PMID: 30643263 Free PMC article. Highly Cited.
RNA velocity of single cells. Gioele La Manno, Ruslan Soldatov, +20 authors, Peter V Kharchenko. less Nature, 2018 Aug 10; 560(7719). PMID: 30089906 Free PMC article. Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma. F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba. less N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992 Free PMC article. Highly Cited.
Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor-induced colitis: a multi-center study. Hamzah Abu-Sbeih, Faisal S Ali, +6 authors, Yinghong Wang. less J Immunother Cancer, 2018 Dec 07; 6(1). PMID: 30518410 Free PMC article.
Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the alpha E beta 7 integrin. K L Cepek, S K Shaw, +4 authors, M B Brenner. less Nature, 1994 Nov 10; 372(6502). PMID: 7969453 Highly Cited.
CXCR3 ligands: redundant, collaborative and antagonistic functions. Joanna R Groom, Andrew D Luster. Immunol Cell Biol, 2011 Jan 12; 89(2). PMID: 21221121 Free PMC article. Highly Cited. Review.
Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Hye Sun Kuehn, Weiming Ouyang, +33 authors, Gulbu Uzel. less Science, 2014 Sep 13; 345(6204). PMID: 25213377 Free PMC article. Highly Cited.
Glucocorticoids in T cell apoptosis and function. M J Herold, K G McPherson, H M Reichardt. Cell Mol Life Sci, 2005 Nov 30; 63(1). PMID: 16314919 Free PMC article. Review.
Budesonide treatment for microscopic colitis from immune checkpoint inhibitors. Michael S Hughes, Gabriel E Molina, +5 authors, Michael Dougan. less J Immunother Cancer, 2019 Nov 09; 7(1). PMID: 31699151 Free PMC article.
Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. Brahma V Kumar, Wenji Ma, +10 authors, Donna L Farber. less Cell Rep, 2017 Sep 21; 20(12). PMID: 28930685 Free PMC article. Highly Cited.
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. Laura M McLane, Mohamed S Abdel-Hakeem, E John Wherry. Annu Rev Immunol, 2019 Jan 25; 37. PMID: 30676822 Highly Cited. Review.
Clonal replacement of tumor-specific T cells following PD-1 blockade. Kathryn E Yost, Ansuman T Satpathy, +13 authors, Howard Y Chang. less Nat Med, 2019 Jul 31; 25(8). PMID: 31359002 Free PMC article. Highly Cited.
Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports. Koji Yoshino, Takayuki Nakayama, +2 authors, Ayumu Ito, Eiichi Sato, Shigehisa Kitano. less BMC Cancer, 2019 Oct 31; 19(1). PMID: 31664934 Free PMC article.
CXCL16/CXCR6 chemokine signaling mediates breast cancer progression by pERK1/2-dependent mechanisms. Gang Xiao, Xiumin Wang, +7 authors, Jianhua Wang. less Oncotarget, 2015 Apr 25; 6(16). PMID: 25909173 Free PMC article.
Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4. Sebastian Zeissig, Britt-Sabina Petersen, +11 authors, Richard S Blumberg. less Gut, 2014 Nov 05; 64(12). PMID: 25367873 Free PMC article.
Targeting immune cell circuits and trafficking in inflammatory bowel disease. Markus F Neurath. Nat Immunol, 2019 Jun 27; 20(8). PMID: 31235952 Highly Cited. Review.
Prediction of gene function by genome-scale expression analysis: prostate cancer-associated genes. M G Walker, W Volkmuth, +2 authors, E Sprinzak, D Hodgson, T Klingler. less Genome Res, 1999 Dec 30; 9(12). PMID: 10613842 Free PMC article.
Cutting edge: CD4 and CD8 T cells are intrinsically different in their proliferative responses. Kathryn E Foulds, Lauren A Zenewicz, +3 authors, Hao Shen. less J Immunol, 2002 Feb 02; 168(4). PMID: 11823476 Highly Cited.
A single-cell molecular map of mouse gastrulation and early organogenesis. Blanca Pijuan-Sala, Jonathan A Griffiths, +13 authors, Berthold Göttgens. less Nature, 2019 Feb 23; 566(7745). PMID: 30787436 Free PMC article. Highly Cited.
PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Michael A Curran, Welby Montalvo, Hideo Yagita, James P Allison. Proc Natl Acad Sci U S A, 2010 Feb 18; 107(9). PMID: 20160101 Free PMC article. Highly Cited.
Cytokines in inflammatory bowel disease. Markus F Neurath. Nat Rev Immunol, 2014 Apr 23; 14(5). PMID: 24751956 Highly Cited. Review.
Fulminant Myocarditis with Combination Immune Checkpoint Blockade. Douglas B Johnson, Justin M Balko, +29 authors, Javid J Moslehi. less N Engl J Med, 2016 Nov 03; 375(18). PMID: 27806233 Free PMC article. Highly Cited.
Tipping the balance: inhibitory checkpoints in intestinal homeostasis. Maria E Joosse, Iris Nederlof, Lucy S K Walker, Janneke N Samsom. Mucosal Immunol, 2018 Dec 01; 12(1). PMID: 30498201 Review.
Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer. Kathryn C Arbour, Laura Mezquita, +16 authors, Matthew D Hellmann. less J Clin Oncol, 2018 Aug 21; 36(28). PMID: 30125216 Highly Cited.
Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Jun Wang, Andreea Ioan-Facsinay, +2 authors, René E M Toes. less Eur J Immunol, 2006 Dec 13; 37(1). PMID: 17154262 Highly Cited.
SCENIC: single-cell regulatory network inference and clustering. Sara Aibar, Carmen Bravo González-Blas, +11 authors, Stein Aerts. less Nat Methods, 2017 Oct 11; 14(11). PMID: 28991892 Free PMC article. Highly Cited.
circlize Implements and enhances circular visualization in R. Zuguang Gu, Lei Gu, +2 authors, Roland Eils, Matthias Schlesner, Benedikt Brors. less Bioinformatics, 2014 Jun 16; 30(19). PMID: 24930139 Highly Cited.
TIGIT: a novel immunotherapy target moving from bench to bedside. Benjamin L Solomon, Ignacio Garrido-Laguna. Cancer Immunol Immunother, 2018 Sep 21; 67(11). PMID: 30232519 Highly Cited. Review.
Time to dissect the autoimmune etiology of cancer antibody immunotherapy. Michael Dougan, Massimo Pietropaolo. J Clin Invest, 2020 Jan 03; 130(1). PMID: 31895048 Free PMC article. Review.
High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma. Alexander T Faje, Donald Lawrence, +5 authors, Ryan J Sullivan. less Cancer, 2018 Jul 06; 124(18). PMID: 29975414 Highly Cited.
Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nathaniel R West, Ahmed N Hegazy, +23 authors, Fiona Powrie. less Nat Med, 2017 Apr 04; 23(5). PMID: 28368383 Free PMC article. Highly Cited.
Tissue-Resident T Cells and Other Resident Leukocytes. David Masopust, Andrew G Soerens. Annu Rev Immunol, 2019 Feb 07; 37. PMID: 30726153 Free PMC article. Highly Cited. Review.
Cytoscape: a software environment for integrated models of biomolecular interaction networks. Paul Shannon, Andrew Markiel, +6 authors, Trey Ideker. less Genome Res, 2003 Nov 05; 13(11). PMID: 14597658 Free PMC article. Highly Cited.
Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways. Bing Huang, Zhanghua Chen, +39 authors, Yuxia Zhang. less Cell, 2019 Nov 16; 179(5). PMID: 31730855
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. Michael A Postow, Jason Chesney, +18 authors, F Stephen Hodi. less N Engl J Med, 2015 Apr 22; 372(21). PMID: 25891304 Free PMC article. Highly Cited.
The Molecular Signatures Database (MSigDB) hallmark gene set collection. Arthur Liberzon, Chet Birger, +3 authors, Pablo Tamayo. less Cell Syst, 2016 Jan 16; 1(6). PMID: 26771021 Free PMC article. Highly Cited.
The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Meghan A Koch, Glady's Tucker-Heard, +3 authors, Daniel J Campbell. less Nat Immunol, 2009 May 05; 10(6). PMID: 19412181 Free PMC article. Highly Cited.
Dimensionality reduction for visualizing single-cell data using UMAP. Etienne Becht, Leland McInnes, +5 authors, Evan W Newell. less Nat Biotechnol, 2018 Dec 12;. PMID: 30531897 Highly Cited.
Deep sequencing of the human TCRγ and TCRβ repertoires suggests that TCRβ rearranges after αβ and γδ T cell commitment. Anna M Sherwood, Cindy Desmarais, +4 authors, Harlan Robins. less Sci Transl Med, 2011 Jul 08; 3(90). PMID: 21734177 Free PMC article.
Checkpoint Blockade Toxicity and Immune Homeostasis in the Gastrointestinal Tract. Michael Dougan. Front Immunol, 2017 Dec 13; 8. PMID: 29230210 Free PMC article. Highly Cited. Review.
Classification of low quality cells from single-cell RNA-seq data. Tomislav Ilicic, Jong Kyoung Kim, +4 authors, Sarah A Teichmann. less Genome Biol, 2016 Feb 19; 17. PMID: 26887813 Free PMC article. Highly Cited.
DoubletFinder: Doublet Detection in Single-Cell RNA Sequencing Data Using Artificial Nearest Neighbors. Christopher S McGinnis, Lyndsay M Murrow, Zev J Gartner. Cell Syst, 2019 Apr 08; 8(4). PMID: 30954475 Free PMC article. Highly Cited.
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. Michael A Postow, Robert Sidlow, Matthew D Hellmann. N Engl J Med, 2018 Jan 11; 378(2). PMID: 29320654 Highly Cited. Review.
Immune checkpoint inhibition-related colitis: symptoms, endoscopic features, histology and response to management. Marnix H Geukes Foppen, Elisa A Rozeman, +8 authors, John B A G Haanen. less ESMO Open, 2018 Feb 02; 3(1). PMID: 29387476 Free PMC article. Highly Cited. Review.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok. less N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431 Free PMC article. Highly Cited.
Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Christopher S Smillie, Moshe Biton, +30 authors, Aviv Regev. less Cell, 2019 Jul 28; 178(3). PMID: 31348891 Free PMC article. Highly Cited.
Colon Immune-Related Adverse Events: Anti-CTLA-4 and Anti-PD-1 Blockade Induce Distinct Immunopathological Entities. Clélia Coutzac, Julien Adam, +17 authors, Nathalie Chaput. less J Crohns Colitis, 2017 Oct 03; 11(10). PMID: 28967957
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981 Free PMC article. Highly Cited.
Lymphocytic colitis-like pattern of mucosal injury and the challenges in diagnosing cancer immunotherapy-related toxicity. Shilpa Grover, Amitabh Srivastava. Cancer, 2019 Mar 21; 125(11). PMID: 30892689
Comprehensive Integration of Single-Cell Data. Tim Stuart, Andrew Butler, +7 authors, Rahul Satija. less Cell, 2019 Jun 11; 177(7). PMID: 31178118 Free PMC article. Highly Cited.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers. Anu Sharma, Sumit K Subudhi, +6 authors, Padmanee Sharma. less Clin Cancer Res, 2018 Jul 29; 25(4). PMID: 30054281 Free PMC article. Highly Cited.
Location, location, location: Tissue resident memory T cells in mice and humans. Peter A Szabo, Michelle Miron, Donna L Farber. Sci Immunol, 2019 Apr 07; 4(34). PMID: 30952804 Free PMC article. Highly Cited. Review.
Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy. Jerome C Martin, Christie Chang, +28 authors, Ephraim Kenigsberg. less Cell, 2019 Sep 03; 178(6). PMID: 31474370 Free PMC article. Highly Cited.
Immune-related adverse events in the gastrointestinal tract: diagnostic utility of upper gastrointestinal biopsies. M Lisa Zhang, Azfar Neyaz, +3 authors, Vikram Deshpande. less Histopathology, 2019 Jul 31; 76(2). PMID: 31361907 Free PMC article.
IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin-directed vascular barrier disruption. Victoria Langer, Eugenia Vivi, +21 authors, Michael Stürzl. less J Clin Invest, 2019 Oct 01; 129(11). PMID: 31566580 Free PMC article.
Revealing the Critical Regulators of Cell Identity in the Mouse Cell Atlas. Shengbao Suo, Qian Zhu, +3 authors, Guo-Cheng Yuan. less Cell Rep, 2018 Nov 08; 25(6). PMID: 30404000 Free PMC article.
Refractory colitis following anti-CTLA4 antibody therapy: analysis of mucosal FOXP3+ T cells. James D Lord, Robert C Hackman, +5 authors, George B McDonald. less Dig Dis Sci, 2009 Jun 10; 55(5). PMID: 19507029 Free PMC article.
Intestinal homeostasis and its breakdown in inflammatory bowel disease. Kevin J Maloy, Fiona Powrie. Nature, 2011 Jun 17; 474(7351). PMID: 21677746 Highly Cited. Review.
Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Paul M Ridker, Jean G MacFadyen, +4 authors, CANTOS Trial Group. less Lancet, 2017 Sep 01; 390(10105). PMID: 28855077 Highly Cited.
Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Stephanie G Downey, Jacob A Klapper, +12 authors, Steven A Rosenberg. less Clin Cancer Res, 2007 Nov 06; 13(22 Pt 1). PMID: 17982122 Free PMC article. Highly Cited.
Concurrent therapy with immune checkpoint inhibitors and TNFα blockade in patients with gastrointestinal immune-related adverse events. Yousef R Badran, Justine V Cohen, +3 authors, Michael Dougan. less J Immunother Cancer, 2019 Aug 24; 7(1). PMID: 31439050 Free PMC article.
Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Makoto Miyara, Yumiko Yoshioka, +15 authors, Shimon Sakaguchi. less Immunity, 2009 May 26; 30(6). PMID: 19464196 Highly Cited.

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Neutrophil: A New Player in Metastatic Cancers. Mengyue Wu, Mutian Ma, +2 authors, Zhenya Tan, Hong Zheng, Xia Liu. less Front Immunol, 2020 Oct 27; 11. PMID: 33101283 Free PMC article. Review.
Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells. Tomokazu S Sumida, Shai Dulberg, +9 authors, David A Hafler. less bioRxiv, 2020 Nov 04;. PMID: 33140047 Free PMC article.
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Use of immune checkpoint inhibitors in cancer patients with pre-existing sarcoidosis. Sang T Kim, Xerxes Pundole, +3 authors, Maria E Suarez-Almazor. less Immunotherapy, 2021 Mar 02; 13(6). PMID: 33641345 Free PMC article.
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From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy. Afshin Derakhshani, Zeinab Rostami, +12 authors, Behzad Baradaran. less Molecules, 2021 May 01; 26(8). PMID: 33920054 Free PMC article. Review.
Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity. Jenna L Collier, Sarah A Weiss, +2 authors, Kristen E Pauken, Debattama R Sen, Arlene H Sharpe. less Nat Immunol, 2021 Jun 19; 22(7). PMID: 34140679 Review.
The Biological Function, Mechanism, and Clinical Significance of m6A RNA Modifications in Head and Neck Carcinoma: A Systematic Review. Feng-Yang Jing, Li-Ming Zhou, +2 authors, Yu-Jie Ning, Xiao-Juan Wang, You-Ming Zhu. less Front Cell Dev Biol, 2021 Jun 18; 9. PMID: 34136491 Free PMC article. Review.
Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells. David Hafler, Tomokazu Sumida, +9 authors, Vijay Kuchroo. less Res Sq, 2021 Jun 16;. PMID: 34127967 Free PMC article.
Single-Cell TCR and Transcriptome Analysis: An Indispensable Tool for Studying T-Cell Biology and Cancer Immunotherapy. Anna Pasetto, Yong-Chen Lu. Front Immunol, 2021 Jun 25; 12. PMID: 34163487 Free PMC article. Review.
Immune checkpoint inhibitor treatment and atherosclerotic cardiovascular disease: an emerging clinical problem. Kikkie Poels, Suzanne I M Neppelenbroek, +3 authors, Tom T P Seijkens. less J Immunother Cancer, 2021 Jun 26; 9(6). PMID: 34168005 Free PMC article. Review.
Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies. Ryan J Sullivan, Jeffrey S Weber. Nat Rev Drug Discov, 2021 Jul 29;. PMID: 34316029 Review.
Single-Cell Transcriptional Survey of Ileal-Anal Pouch Immune Cells From Ulcerative Colitis Patients. Joseph C Devlin, Jordan Axelrad, +7 authors, P'ng Loke. less Gastroenterology, 2020 Dec 29; 160(5). PMID: 33359089 Free PMC article.
Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events. Bilal A Siddiqui, Jinesh S Gheeya, +16 authors, Nizar Tannir. less J Immunother Cancer, 2021 Jul 31; 9(7). PMID: 34326169 Free PMC article.
Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease. Alexa R Weingarden, Samuel J S Rubin, John Gubatan. World J Gastrointest Oncol, 2021 Aug 31; 13(8). PMID: 34457186 Free PMC article. Review.
The precursors of CD8+ tissue resident memory T cells: from lymphoid organs to infected tissues. Lianne Kok, David Masopust, Ton N Schumacher. Nat Rev Immunol, 2021 Sep 05; 22(5). PMID: 34480118 Free PMC article. Review.
Trends in the Research Into Immune Checkpoint Blockade by Anti-PD1/PDL1 Antibodies in Cancer Immunotherapy: A Bibliometric Study. Yiting Sun, Liqing Jiang, +8 authors, Zhi Li. less Front Pharmacol, 2021 Sep 08; 12. PMID: 34489691 Free PMC article.
CXCR6 is required for antitumor efficacy of intratumoral CD8+ T cell. Binglin Wang, Yi Wang, +9 authors, Yang Sun. less J Immunother Cancer, 2021 Sep 01; 9(8). PMID: 34462326 Free PMC article.
Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer. Tanya E Keenan, Jennifer L Guerriero, +26 authors, Sara M Tolaney. less Nat Commun, 2021 Sep 23; 12(1). PMID: 34548479 Free PMC article.
Inhibition of CDK4/6 Promotes CD8 T-cell Memory Formation. Max Heckler, Lestat R Ali, +21 authors, Stephanie K Dougan. less Cancer Discov, 2021 May 05; 11(10). PMID: 33941591 Free PMC article.
Interferon-Gamma-Producing CD8+ Tissue Resident Memory T Cells Are a Targetable Hallmark of Immune Checkpoint Inhibitor-Colitis. Sarah C Sasson, Stephanie M Slevin, +24 authors, Oliver Brain. less Gastroenterology, 2021 Jun 21; 161(4). PMID: 34147519 Free PMC article.
Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis. Harm Westdorp, Mark W D Sweep, +8 authors, I Jolanda M de Vries. less Front Immunol, 2021 Nov 16; 12. PMID: 34777387 Free PMC article. Review.
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The foundations of immune checkpoint blockade and the ipilimumab approval decennial. Alan J Korman, Sarah C Garrett-Thomson, Nils Lonberg. Nat Rev Drug Discov, 2021 Dec 24;. PMID: 34937915 Review.
huARdb: human Antigen Receptor database for interactive clonotype-transcriptome analysis at the single-cell level. Lize Wu, Ziwei Xue, +10 authors, Wanlu Liu. less Nucleic Acids Res, 2021 Oct 05; 50(D1). PMID: 34606616 Free PMC article.
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Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy. Marie Siwicki, Nicolas A Gort-Freitas, +33 authors, Mikael J Pittet. less Sci Immunol, 2021 Jul 04; 6(61). PMID: 34215680 Free PMC article.
Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells. Tomokazu S Sumida, Shai Dulberg, +9 authors, David A Hafler. less Nat Immunol, 2022 Mar 19; 23(4). PMID: 35301508 Free PMC article.
Single-cell transcriptomic analysis of human colonic macrophages reveals niche-specific subsets. Diana Domanska, Umair Majid, +5 authors, Frode L Jahnsen. less J Exp Med, 2022 Feb 10; 219(3). PMID: 35139155 Free PMC article.
Integrative analysis of gut microbiome and host transcriptomes reveals associations between treatment outcomes and immunotherapy-induced colitis. Toshiharu Sakurai, Marco A De Velasco, +9 authors, Masatoshi Kudo. less Mol Oncol, 2021 Jul 17; 16(7). PMID: 34270845 Free PMC article.
Evaluation of the TCR Repertoire as a Predictive and Prognostic Biomarker in Cancer: Diversity or Clonality? Andrea Aran, Laia Garrigós, +2 authors, Giuseppe Curigliano, Javier Cortés, Mercè Martí. less Cancers (Basel), 2022 Apr 13; 14(7). PMID: 35406543 Free PMC article. Review.
Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events. Remo Poto, Teresa Troiani, +4 authors, Gilda Varricchi. less Front Immunol, 2022 Apr 19; 13. PMID: 35432346 Free PMC article. Review.
The Genomic Profile Associated with Risk of Severe Forms of COVID-19 in Amazonian Native American Populations. Lucas Favacho Pastana, Thays Amâncio Silva, +19 authors, Ney Pereira Carneiro Dos Santos. less J Pers Med, 2022 Apr 24; 12(4). PMID: 35455670 Free PMC article.
Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy. Sang T Kim, Yanshuo Chu, +35 authors, Roza Nurieva. less Nat Commun, 2022 Apr 14; 13(1). PMID: 35413951 Free PMC article.
Exploring the Mechanisms Underlying the Cardiotoxic Effects of Immune Checkpoint Inhibitor Therapies. Daniel Ronen, Aseel Bsoul, +4 authors, Rabea Asleh. less Vaccines (Basel), 2022 Apr 24; 10(4). PMID: 35455289 Free PMC article. Review.
AXL targeting restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through expansion of TCF1+ CD8 T cells. Huiyu Li, Zhida Liu, +30 authors, Rolf A Brekken. less Cell Rep Med, 2022 May 03; 3(3). PMID: 35492873 Free PMC article.
Targeting HIF-1α abrogates PD-L1-mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues. Christopher M Bailey, Yan Liu, +5 authors, Yin Wang. less J Clin Invest, 2022 Mar 04; 132(9). PMID: 35239514 Free PMC article.
Tissue-resident memory T cells in gastrointestinal cancer immunology and immunotherapy: ready for prime time? Syrine Abdeljaoued, Sara Arfa, +6 authors, Christophe Borg. less J Immunother Cancer, 2022 Apr 27; 10(4). PMID: 35470231 Free PMC article. Review.
Treatment of patients with cancer using PD‑1/PD‑L1 antibodies: Adverse effects and management strategies (Review). Guangshun Sun, Hanyuan Liu, +9 authors, Guoqiang Shao. less Int J Oncol, 2022 Apr 30; 60(6). PMID: 35485291 Free PMC article. Review.
Extricating human tumour immune alterations from tissue inflammation. Florian Mair, Jami R Erickson, +9 authors, Martin Prlic. less Nature, 2022 May 12; 605(7911). PMID: 35545675

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