Journal Article
. 2016 Sep; 166(6):1500-1511.e9.
doi: 10.1016/j.cell.2016.08.052.

A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells

Meromit Singer 1 Chao Wang 2 Le Cong 1 Nemanja D Marjanovic 3 Monika S Kowalczyk 1 Huiyuan Zhang 2 Jackson Nyman 1 Kaori Sakuishi 2 Sema Kurtulus 2 David Gennert 1 Junrong Xia 2 John Y H Kwon 1 James Nevin 2 Rebecca H Herbst 1 Itai Yanai 4 Orit Rozenblatt-Rosen 1 Vijay K Kuchroo 5 Aviv Regev 6 Ana C Anderson 7 
Affiliations
  • PMID: 27610572
  •     37 References
  •     165 citations

Abstract

Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8(+) tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and we use CRISPR-Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8(+) TILs. Our results open novel avenues for targeting dysfunctional T cell states while leaving activation programs intact.

Keywords: CD8; CRISPR/Cas9; Gata-3; T cell; TILs; cancer; dysfunction; exhaustion; metallothioneins; single-cell; tumor; zinc.

Zinc and its role in immunity and inflammation.
Paola Bonaventura, Giulia Benedetti, Francis Albarède, Pierre Miossec.
Autoimmun Rev, 2014 Dec 03; 14(4). PMID: 25462582
Highly Cited. Review.
The three main stumbling blocks for anticancer T cells.
Lukas Baitsch, Silvia A Fuertes-Marraco, +2 authors, Daniel E Speiser.
Trends Immunol, 2012 Mar 27; 33(7). PMID: 22445288
Review.
Maps of random walks on complex networks reveal community structure.
Martin Rosvall, Carl T Bergstrom.
Proc Natl Acad Sci U S A, 2008 Jan 25; 105(4). PMID: 18216267    Free PMC article.
Highly Cited. Review.
Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles.
Aravind Subramanian, Pablo Tamayo, +8 authors, Jill P Mesirov.
Proc Natl Acad Sci U S A, 2005 Oct 04; 102(43). PMID: 16199517    Free PMC article.
Highly Cited.
Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer.
Junko Matsuzaki, Sacha Gnjatic, +9 authors, Kunle Odunsi.
Proc Natl Acad Sci U S A, 2010 Apr 14; 107(17). PMID: 20385810    Free PMC article.
Highly Cited.
Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates.
Surojit Sarkar, Vandana Kalia, +3 authors, Rafi Ahmed.
J Exp Med, 2008 Mar 05; 205(3). PMID: 18316415    Free PMC article.
Highly Cited.
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome.
Bo Li, Colin N Dewey.
BMC Bioinformatics, 2011 Aug 06; 12. PMID: 21816040    Free PMC article.
Highly Cited.
In vivo genome editing using Staphylococcus aureus Cas9.
F Ann Ran, Le Cong, +10 authors, Feng Zhang.
Nature, 2015 Apr 02; 520(7546). PMID: 25830891    Free PMC article.
Highly Cited.
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
Shawn D Blackburn, Haina Shin, +7 authors, E John Wherry.
Nat Immunol, 2008 Dec 02; 10(1). PMID: 19043418    Free PMC article.
Highly Cited.
Stable inhibitory activity of regulatory T cells requires the transcription factor Helios.
Hye-Jung Kim, R Anthony Barnitz, +10 authors, Harvey Cantor.
Science, 2015 Oct 17; 350(6258). PMID: 26472910    Free PMC article.
Highly Cited.
Inhibitory Receptors Beyond T Cell Exhaustion.
Silvia A Fuertes Marraco, Natalie J Neubert, Grégory Verdeil, Daniel E Speiser.
Front Immunol, 2015 Jul 15; 6. PMID: 26167163    Free PMC article.
Highly Cited. Review.
Comprehensive Classification of Retinal Bipolar Neurons by Single-Cell Transcriptomics.
Karthik Shekhar, Sylvain W Lapan, +11 authors, Joshua R Sanes.
Cell, 2016 Aug 28; 166(5). PMID: 27565351    Free PMC article.
Highly Cited.
GenePattern 2.0.
Michael Reich, Ted Liefeld, +3 authors, Jill P Mesirov.
Nat Genet, 2006 Apr 28; 38(5). PMID: 16642009
Highly Cited.
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity.
Kaori Sakuishi, Lionel Apetoh, +3 authors, Ana C Anderson.
J Exp Med, 2010 Sep 08; 207(10). PMID: 20819927    Free PMC article.
Highly Cited.
Smart-seq2 for sensitive full-length transcriptome profiling in single cells.
Simone Picelli, Åsa K Björklund, +3 authors, Rickard Sandberg.
Nat Methods, 2013 Sep 24; 10(11). PMID: 24056875
Highly Cited.
Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation.
Ana C Anderson, Nicole Joller, Vijay K Kuchroo.
Immunity, 2016 May 19; 44(5). PMID: 27192565    Free PMC article.
Highly Cited. Review.
Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients.
Lukas Baitsch, Petra Baumgaertner, +9 authors, Daniel E Speiser.
J Clin Invest, 2011 May 11; 121(6). PMID: 21555851    Free PMC article.
Highly Cited.
Adjusting batch effects in microarray expression data using empirical Bayes methods.
W Evan Johnson, Cheng Li, Ariel Rabinovic.
Biostatistics, 2006 Apr 25; 8(1). PMID: 16632515
Highly Cited.
Molecular signature of CD8+ T cell exhaustion during chronic viral infection.
E John Wherry, Sang-Jun Ha, +7 authors, Rafi Ahmed.
Immunity, 2007 Oct 24; 27(4). PMID: 17950003
Highly Cited.
Genome-scale CRISPR-Cas9 knockout screening in human cells.
Ophir Shalem, Neville E Sanjana, +8 authors, Feng Zhang.
Science, 2013 Dec 18; 343(6166). PMID: 24336571    Free PMC article.
Highly Cited.
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Ben Langmead, Cole Trapnell, Mihai Pop, Steven L Salzberg.
Genome Biol, 2009 Mar 06; 10(3). PMID: 19261174    Free PMC article.
Highly Cited.
Features of responding T cells in cancer and chronic infection.
Peter S Kim, Rafi Ahmed.
Curr Opin Immunol, 2010 Mar 09; 22(2). PMID: 20207527    Free PMC article.
Highly Cited. Review.
Acquired resistance to immunotherapy and future challenges.
Nicholas P Restifo, Mark J Smyth, Alexandra Snyder.
Nat Rev Cancer, 2016 Jan 30; 16(2). PMID: 26822578    Free PMC article.
Highly Cited.
Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells.
Alex K Shalek, Rahul Satija, +15 authors, Aviv Regev.
Nature, 2013 May 21; 498(7453). PMID: 23685454    Free PMC article.
Highly Cited.
Molecular and cellular insights into T cell exhaustion.
E John Wherry, Makoto Kurachi.
Nat Rev Immunol, 2015 Jul 25; 15(8). PMID: 26205583    Free PMC article.
Highly Cited. Review.
Multiplex genome engineering using CRISPR/Cas systems.
Le Cong, F Ann Ran, +8 authors, Feng Zhang.
Science, 2013 Jan 05; 339(6121). PMID: 23287718    Free PMC article.
Highly Cited.
Metallothionein.
D H Hamer.
Annu Rev Biochem, 1986 Jan 01; 55. PMID: 3527054
Highly Cited. Review.
Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients.
Julien Fourcade, Zhaojun Sun, +6 authors, Hassane M Zarour.
J Exp Med, 2010 Sep 08; 207(10). PMID: 20819923    Free PMC article.
Highly Cited.
Innate and Adaptive Immune Regulation During Chronic Viral Infections.
Elina I Zuniga, Monica Macal, Gavin M Lewis, James A Harker.
Annu Rev Virol, 2016 Mar 10; 2(1). PMID: 26958929    Free PMC article.
Highly Cited. Review.
GO-PCA: An Unsupervised Method to Explore Gene Expression Data Using Prior Knowledge.
Florian Wagner.
PLoS One, 2015 Nov 18; 10(11). PMID: 26575370    Free PMC article.
Molecular profiling of CD8 T cells in autochthonous melanoma identifies Maf as driver of exhaustion.
Marilyn Giordano, Coralie Henin, +10 authors, Grégory Verdeil.
EMBO J, 2015 Jul 04; 34(15). PMID: 26139534    Free PMC article.
Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory.
Travis A Doering, Alison Crawford, +3 authors, E John Wherry.
Immunity, 2012 Nov 20; 37(6). PMID: 23159438    Free PMC article.
Highly Cited.
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.
Itay Tirosh, Benjamin Izar, +34 authors, Levi A Garraway.
Science, 2016 Apr 29; 352(6282). PMID: 27124452    Free PMC article.
Highly Cited.
GATA-3 function in innate and adaptive immunity.
Irma Tindemans, Nicolas Serafini, James P Di Santo, Rudi W Hendriks.
Immunity, 2014 Aug 26; 41(2). PMID: 25148023
Highly Cited. Review.
Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia.
Qing Zhou, Meghan E Munger, +8 authors, Bruce R Blazar.
Blood, 2011 Mar 10; 117(17). PMID: 21385853    Free PMC article.
Highly Cited.
Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity.
Jellert T Gaublomme, Nir Yosef, +10 authors, Aviv Regev.
Cell, 2015 Nov 27; 163(6). PMID: 26607794    Free PMC article.
Highly Cited.
Discovering motifs in ranked lists of DNA sequences.
Eran Eden, Doron Lipson, Sivan Yogev, Zohar Yakhini.
PLoS Comput Biol, 2007 Mar 27; 3(3). PMID: 17381235    Free PMC article.
Highly Cited.
Probing the Diversity of T Cell Dysfunction in Cancer.
Ryan T Sowell, Susan M Kaech.
Cell, 2016 Sep 10; 166(6). PMID: 27610560    Free PMC article.
Genome Informatics 2016.
Davide Chicco, Michael M Hoffman.
Genome Biol, 2017 Jan 18; 18(1). PMID: 28093077    Free PMC article.
The Principles of Engineering Immune Cells to Treat Cancer.
Wendell A Lim, Carl H June.
Cell, 2017 Feb 12; 168(4). PMID: 28187291    Free PMC article.
Highly Cited. Review.
Low-dose controlled release of mTOR inhibitors maintains T cell plasticity and promotes central memory T cells.
Joshua M Gammon, Emily A Gosselin, +4 authors, Christopher M Jewell.
J Control Release, 2017 Mar 05; 263. PMID: 28257991    Free PMC article.
Co-inhibitory blockade while preserving tolerance: checkpoint inhibitors for glioblastoma.
Liliana E Lucca, David A Hafler.
Immunol Rev, 2017 Mar 05; 276(1). PMID: 28258696    Free PMC article.
Review.
Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies.
Kristin G Anderson, Ingunn M Stromnes, Philip D Greenberg.
Cancer Cell, 2017 Mar 16; 31(3). PMID: 28292435    Free PMC article.
Highly Cited. Review.
Partners in Crime: Combining Oncolytic Viroimmunotherapy with Other Therapies.
Masataka Suzuki.
Mol Ther, 2017 Mar 24; 25(4). PMID: 28330695    Free PMC article.
The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection.
Howell F Moffett, Adam N R Cartwright, +11 authors, Kai W Wucherpfennig.
Nat Immunol, 2017 May 23; 18(7). PMID: 28530712    Free PMC article.
Cancer immunotherapy by targeting immune checkpoints: mechanism of T cell dysfunction in cancer immunity and new therapeutic targets.
Hwei-Fang Tsai, Ping-Ning Hsu.
J Biomed Sci, 2017 May 27; 24(1). PMID: 28545567    Free PMC article.
Review.
Novel "Elements" of Immune Suppression within the Tumor Microenvironment.
Devikala Gurusamy, David Clever, Robert Eil, Nicholas P Restifo.
Cancer Immunol Res, 2017 Jun 04; 5(6). PMID: 28576921    Free PMC article.
Review.
Transcriptional and epigenetic regulation of T cell hyporesponsiveness.
Renata M Pereira, Patrick G Hogan, Anjana Rao, Gustavo J Martinez.
J Leukoc Biol, 2017 Jun 14; 102(3). PMID: 28606939    Free PMC article.
Review.
Mammalian synthetic biology in the age of genome editing and personalized medicine.
Patrick Ho, Yvonne Y Chen.
Curr Opin Chem Biol, 2017 Jun 20; 40. PMID: 28628856    Free PMC article.
Review.
Blockade of only TGF-β 1 and 2 is sufficient to enhance the efficacy of vaccine and PD-1 checkpoint blockade immunotherapy.
Masaki Terabe, Faith C Robertson, +6 authors, Jay A Berzofsky.
Oncoimmunology, 2017 Jun 24; 6(5). PMID: 28638730    Free PMC article.
Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.
Carlos R Gil Del Alcazar, Sung Jin Huh, +27 authors, Kornelia Polyak.
Cancer Discov, 2017 Jun 28; 7(10). PMID: 28652380    Free PMC article.
Highly Cited.
Molecular Dissection of CD8+ T-Cell Dysfunction.
Chao Wang, Meromit Singer, Ana C Anderson.
Trends Immunol, 2017 Jul 01; 38(8). PMID: 28662970    Free PMC article.
Review.
Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer.
Clemence Granier, Eleonore De Guillebon, +7 authors, Eric Tartour.
ESMO Open, 2017 Aug 02; 2(2). PMID: 28761757    Free PMC article.
Highly Cited. Review.
Unravelling biology and shifting paradigms in cancer with single-cell sequencing.
Timour Baslan, James Hicks.
Nat Rev Cancer, 2017 Aug 25; 17(9). PMID: 28835719
Highly Cited. Review.
Tim-3, Lag-3, and TIGIT.
Nicole Joller, Vijay K Kuchroo.
Curr Top Microbiol Immunol, 2017 Sep 14; 410. PMID: 28900677    Free PMC article.
Review.
The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation.
Antonia Wallrapp, Samantha J Riesenfeld, +20 authors, Vijay K Kuchroo.
Nature, 2017 Sep 14; 549(7672). PMID: 28902842    Free PMC article.
Highly Cited.
Regulation of mTOR, Metabolic Fitness, and Effector Functions by Cytokines in Natural Killer Cells.
Sébastien Viel, Laurie Besson, +2 authors, Antoine Marçais.
Cancers (Basel), 2017 Sep 29; 9(10). PMID: 28956813    Free PMC article.
Review.
Single-cell transcriptomics to explore the immune system in health and disease.
Michael J T Stubbington, Orit Rozenblatt-Rosen, Aviv Regev, Sarah A Teichmann.
Science, 2017 Oct 07; 358(6359). PMID: 28983043    Free PMC article.
Highly Cited. Review.
The diverse functions of the PD1 inhibitory pathway.
Arlene H Sharpe, Kristen E Pauken.
Nat Rev Immunol, 2017 Oct 11; 18(3). PMID: 28990585
Highly Cited. Review.
Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche.
Vesselin T Tomov, Olesya Palko, +10 authors, E John Wherry.
Immunity, 2017 Oct 17; 47(4). PMID: 29031786    Free PMC article.
Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8+ T Cell Responses to Chronic Viral Infections and Cancer.
Isobel S Okoye, Michael Houghton, +2 authors, Shokrollah Elahi.
Front Immunol, 2017 Oct 17; 8. PMID: 29033936    Free PMC article.
Review.
Early Transcriptional Divergence Marks Virus-Specific Primary Human CD8+ T Cells in Chronic versus Acute Infection.
David Wolski, Peter K Foote, +17 authors, Georg M Lauer.
Immunity, 2017 Oct 19; 47(4). PMID: 29045899    Free PMC article.
Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor.
Tomasz Maj, Wei Wang, +11 authors, Weiping Zou.
Nat Immunol, 2017 Oct 31; 18(12). PMID: 29083399    Free PMC article.
Highly Cited.
Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data.
Julien Racle, Kaat de Jonge, +2 authors, David Gfeller.
Elife, 2017 Nov 14; 6. PMID: 29130882    Free PMC article.
Highly Cited.
The Human Cell Atlas.
Aviv Regev, Sarah A Teichmann, +59 authors, Human Cell Atlas Meeting Participants.
Elife, 2017 Dec 06; 6. PMID: 29206104    Free PMC article.
Highly Cited.
Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours.
J Justin Milner, Clara Toma, +10 authors, Ananda W Goldrath.
Nature, 2017 Dec 07; 552(7684). PMID: 29211713    Free PMC article.
Highly Cited.
Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4+ T Cell Dysfunction.
Jie Wu, Hedong Zhang, +9 authors, Wenhao Chen.
Immunity, 2017 Dec 10; 47(6). PMID: 29221730    Free PMC article.
Mixed signature of activation and dysfunction allows human decidual CD8+ T cells to provide both tolerance and immunity.
Anita van der Zwan, Kevin Bi, +4 authors, Tamara Tilburgs.
Proc Natl Acad Sci U S A, 2017 Dec 21; 115(2). PMID: 29259116    Free PMC article.
PD-1 expression on tumor-specific T cells: Friend or foe for immunotherapy?
Sylvain Simon, Nathalie Labarriere.
Oncoimmunology, 2018 Jan 04; 7(1). PMID: 29296515    Free PMC article.
Highly Cited. Review.
Modeling tumor immunity of mouse glioblastoma by exhausted CD8+ T cells.
Hiroshi Nakashima, Quazim A Alayo, +6 authors, E Antonio Chiocca.
Sci Rep, 2018 Jan 11; 8(1). PMID: 29317703    Free PMC article.
Epigenetic control of CD8+ T cell differentiation.
Amanda N Henning, Rahul Roychoudhuri, Nicholas P Restifo.
Nat Rev Immunol, 2018 Jan 31; 18(5). PMID: 29379213    Free PMC article.
Highly Cited. Review.
NK Cells and γδT Cells for Relapse Protection After Allogeneic Hematopoietic Cell Transplantation (HCT).
Moniek A de Witte, Jürgen Kuball, Jeffrey S Miller.
Curr Stem Cell Rep, 2018 Feb 06; 3(4). PMID: 29399441    Free PMC article.
14-3-3ζ delivered by hepatocellular carcinoma-derived exosomes impaired anti-tumor function of tumor-infiltrating T lymphocytes.
Xiaochen Wang, Haiyuan Shen, +9 authors, Xiaojie Lu.
Cell Death Dis, 2018 Feb 09; 9(2). PMID: 29415983    Free PMC article.
Early Reconstitution of NK and γδ T Cells and Its Implication for the Design of Post-Transplant Immunotherapy.
Moniek A de Witte, Dhifaf Sarhan, +8 authors, Jeffrey S Miller.
Biol Blood Marrow Transplant, 2018 Mar 06; 24(6). PMID: 29505821    Free PMC article.
The impact of single-cell RNA sequencing on understanding the functional organization of the immune system.
Peter Vegh, Muzlifah Haniffa.
Brief Funct Genomics, 2018 Mar 17; 17(4). PMID: 29547972    Free PMC article.
Review.
Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer.
Wei Li, Takashi Tanikawa, +15 authors, Weiping Zou.
Cell Metab, 2018 May 29; 28(1). PMID: 29805099    Free PMC article.
Highly Cited.
A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade.
Daniela S Thommen, Viktor H Koelzer, +16 authors, Alfred Zippelius.
Nat Med, 2018 Jun 13; 24(7). PMID: 29892065    Free PMC article.
Highly Cited.
Induction and transcriptional regulation of the co-inhibitory gene module in T cells.
Norio Chihara, Asaf Madi, +18 authors, Vijay K Kuchroo.
Nature, 2018 Jun 15; 558(7710). PMID: 29899446    Free PMC article.
Highly Cited.
Immune Checkpoint-Mediated Interactions Between Cancer and Immune Cells in Prostate Adenocarcinoma and Melanoma.
Angela Rita Elia, Sara Caputo, Matteo Bellone.
Front Immunol, 2018 Aug 16; 9. PMID: 30108594    Free PMC article.
Review.
Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted.
Jeremy S Tilstra, Lyndsay Avery, +6 authors, Mark J Shlomchik.
J Clin Invest, 2018 Aug 22; 128(11). PMID: 30130253    Free PMC article.
Human breast tumor-infiltrating CD8+ T cells retain polyfunctionality despite PD-1 expression.
Colt A Egelston, Christian Avalos, +9 authors, Peter P Lee.
Nat Commun, 2018 Oct 18; 9(1). PMID: 30327458    Free PMC article.
Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort.
Qinchuan Wang, Justin R Gregg, +7 authors, Xifeng Wu.
Oncoimmunology, 2018 Dec 14; 8(1). PMID: 30546938    Free PMC article.
The pursuit of transplantation tolerance: new mechanistic insights.
Pawan K Gupta, Christine M McIntosh, Anita S Chong, Maria-Luisa Alegre.
Cell Mol Immunol, 2019 Feb 15; 16(4). PMID: 30760917    Free PMC article.
Combinatorial prediction of marker panels from single-cell transcriptomic data.
Conor Delaney, Alexandra Schnell, +4 authors, Meromit Singer.
Mol Syst Biol, 2019 Oct 28; 15(10). PMID: 31657111    Free PMC article.
A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer.
Xi Li, Rouzheng Wang, +25 authors, Tao Dong.
Front Oncol, 2019 Nov 12; 9. PMID: 31709176    Free PMC article.
The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality.
Chaofan Li, Bibo Zhu, +18 authors, Jie Sun.
Immunity, 2019 Sep 19; 51(3). PMID: 31533057    Free PMC article.
Highly Cited.
Spatiotemporally Skewed Activation of Programmed Cell Death Receptor 1-Positive T Cells after Epstein-Barr Virus Infection and Tumor Development in Long-Term Fully Humanized Mice.
Simon Danisch, Constanze Slabik, +15 authors, Renata Stripecke.
Am J Pathol, 2018 Dec 30; 189(3). PMID: 30593822    Free PMC article.
Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy.
Jun Wei, Lingyun Long, +14 authors, Hongbo Chi.
Nature, 2019 Dec 13; 576(7787). PMID: 31827283    Free PMC article.
Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment.
Yangjing Zhao, Qixiang Shao, Guangyong Peng.
Cell Mol Immunol, 2019 Dec 20; 17(1). PMID: 31853000    Free PMC article.
Review.
Pediatric patients with acute lymphoblastic leukemia generate abundant and functional neoantigen-specific CD8+ T cell responses.
Anthony E Zamora, Jeremy Chase Crawford, +17 authors, Paul G Thomas.
Sci Transl Med, 2019 Jun 28; 11(498). PMID: 31243155    Free PMC article.
Integrative network modeling reveals mechanisms underlying T cell exhaustion.
Hamid Bolouri, Mary Young, +12 authors, Alexander Ratushny.
Sci Rep, 2020 Feb 07; 10(1). PMID: 32024856    Free PMC article.
Single-cell analysis of human adipose tissue identifies depot and disease specific cell types.
Jinchu Vijay, Marie-Frédérique Gauthier, +18 authors, Elin Grundberg.
Nat Metab, 2020 Feb 19; 2(1). PMID: 32066997    Free PMC article.
Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells.
Matthew B Dong, Guangchuan Wang, +17 authors, Sidi Chen.
Cell, 2019 Aug 24; 178(5). PMID: 31442407    Free PMC article.
Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment.
Elham Azizi, Ambrose J Carr, +16 authors, Dana Pe'er.
Cell, 2018 Jul 03; 174(5). PMID: 29961579    Free PMC article.
Highly Cited.
Efficient CRISPR/Cas9-Mediated Mutagenesis in Primary Murine T Lymphocytes.
Bonnie Huang, Kristoffer Haurum Johansen, Pamela L Schwartzberg.
Curr Protoc Immunol, 2018 Oct 13; 124(1). PMID: 30312021    Free PMC article.
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells.
Sema Kurtulus, Asaf Madi, +10 authors, Ana C Anderson.
Immunity, 2019 Jan 13; 50(1). PMID: 30635236    Free PMC article.
Highly Cited.
Revolutionizing Cancer Immunology: The Power of Next-Generation Sequencing Technologies.
Meromit Singer, Ana C Anderson.
Cancer Immunol Res, 2019 Feb 03; 7(2). PMID: 30709909    Free PMC article.
Review.
Therapeutic Cancer Vaccines-T Cell Responses and Epigenetic Modulation.
Apriliana E R Kartikasari, Monica D Prakash, +4 authors, Magdalena Plebanski.
Front Immunol, 2019 Feb 12; 9. PMID: 30740111    Free PMC article.
Review.
Multiplexed enrichment and genomic profiling of peripheral blood cells reveal subset-specific immune signatures.
Miguel Reyes, Dwayne Vickers, +6 authors, Paul C Blainey.
Sci Adv, 2019 Feb 13; 5(1). PMID: 30746468    Free PMC article.
A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPα expression.
Lara M Myers, Michal Caspi Tal, +17 authors, Kim J Hasenkrug.
Nat Commun, 2019 Feb 17; 10(1). PMID: 30770827    Free PMC article.
Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.
Xindong Liu, Yun Wang, +26 authors, Chen Dong.
Nature, 2019 Mar 01; 567(7749). PMID: 30814730    Free PMC article.
Highly Cited.
Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen.
Stefanie K Wculek, Joaquín Amores-Iniesta, +3 authors, David Sancho.
J Immunother Cancer, 2019 Apr 10; 7(1). PMID: 30961656    Free PMC article.
Highly Cited.
Computational approaches for characterizing the tumor immune microenvironment.
Candace C Liu, Chloé B Steen, Aaron M Newman.
Immunology, 2019 Jul 28; 158(2). PMID: 31347163    Free PMC article.
Review.
Treg Cells Promote the SREBP1-Dependent Metabolic Fitness of Tumor-Promoting Macrophages via Repression of CD8+ T Cell-Derived Interferon-γ.
Chang Liu, Maria Chikina, +13 authors, Dario A A Vignali.
Immunity, 2019 Jul 28; 51(2). PMID: 31350177    Free PMC article.
Highly Cited.
Co-Stimulatory Receptors in Cancers and Their Implications for Cancer Immunotherapy.
Seongju Jeong, Su-Hyung Park.
Immune Netw, 2020 Mar 12; 20(1). PMID: 32158591    Free PMC article.
Review.
The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity.
Alexandra Schnell, Lloyd Bod, Asaf Madi, Vijay K Kuchroo.
Cell Res, 2020 Jan 25; 30(4). PMID: 31974523    Free PMC article.
Review.
UV radiation recruits CD4+GATA3+ and CD8+GATA3+ T cells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo.
Nathan J Hawkshaw, Suzanne M Pilkington, +5 authors, Lesley E Rhodes.
Clin Transl Immunology, 2020 Apr 08; 9(4). PMID: 32257209    Free PMC article.
Differentiated agonistic antibody targeting CD137 eradicates large tumors without hepatotoxicity.
Ugur Eskiocak, Wilson Guzman, +21 authors, Robert Tighe.
JCI Insight, 2020 Mar 13; 5(5). PMID: 32161196    Free PMC article.
4-1BB Delineates Distinct Activation Status of Exhausted Tumor-Infiltrating CD8+ T Cells in Hepatocellular Carcinoma.
Hyung-Don Kim, Seongyeol Park, +15 authors, Su-Hyung Park.
Hepatology, 2019 Jul 30; 71(3). PMID: 31353502    Free PMC article.
Towards multiscale modeling of the CD8+ T cell response to viral infections.
Subhasish Baral, Rubesh Raja, Pramita Sen, Narendra M Dixit.
Wiley Interdiscip Rev Syst Biol Med, 2019 Feb 28; 11(4). PMID: 30811096    Free PMC article.
Review.
Tissue Cytokine IL-33 Modulates the Cytotoxic CD8 T Lymphocyte Activity During Nutrient Deprivation by Regulation of Lineage-Specific Differentiation Programs.
Caroline Dreis, Florian M Ottenlinger, +5 authors, Heinfried H Radeke.
Front Immunol, 2019 Aug 10; 10. PMID: 31396219    Free PMC article.
Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-Seq.
Santiago J Carmona, Imran Siddiqui, +2 authors, David Gfeller.
Oncoimmunology, 2020 Apr 22; 9(1). PMID: 32313720    Free PMC article.
Ushering in Integrated T Cell Repertoire Profiling in Cancer.
Ning Jiang, Alexandra A Schonnesen, Ke-Yue Ma.
Trends Cancer, 2019 Feb 14; 5(2). PMID: 30755308    Free PMC article.
Review.
Transcriptomic Profiling of Tumor-Infiltrating CD4+TIM-3+ T Cells Reveals Their Suppressive, Exhausted, and Metastatic Characteristics in Colorectal Cancer Patients.
Varun Sasidharan Nair, Salman M Toor, +8 authors, Eyad Elkord.
Vaccines (Basel), 2020 Feb 12; 8(1). PMID: 32041340    Free PMC article.
VISTA: a novel immunotherapy target for normalizing innate and adaptive immunity.
Mohamed A ElTanbouly, Walburga Croteau, Randolph J Noelle, J Louise Lines.
Semin Immunol, 2019 Oct 13; 42. PMID: 31604531    Free PMC article.
Review.
The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies.
Florent Petitprez, Maxime Meylan, +2 authors, Wolf H Fridman.
Front Immunol, 2020 May 28; 11. PMID: 32457745    Free PMC article.
Review.
Tracking the immune response with single-cell genomics.
Kathryn E Yost, Howard Y Chang, Ansuman T Satpathy.
Vaccine, 2019 Dec 21; 38(28). PMID: 31859202    Free PMC article.
Chromatin Priming Renders T Cell Tolerance-Associated Genes Sensitive to Activation below the Signaling Threshold for Immune Response Genes.
Sarah L Bevington, Sky T H Ng, +3 authors, Peter N Cockerill.
Cell Rep, 2020 Jun 11; 31(10). PMID: 32521273    Free PMC article.
Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch.
Wen Juan Tu, Robert D McCuaig, +14 authors, Sudha Rao.
Front Immunol, 2020 Jul 03; 11. PMID: 32612611    Free PMC article.
Human cancer germline antigen-specific cytotoxic T cell-what can we learn from patient.
Megat Abd Hamid, Yanchun Peng, Tao Dong.
Cell Mol Immunol, 2020 May 27; 17(7). PMID: 32451453    Free PMC article.
Review.
The Dysfunctional Immune System in Common Variable Immunodeficiency Increases the Susceptibility to Gastric Cancer.
Irene Gullo, Catarina Costa, +14 authors, Ana E Sousa.
Cells, 2020 Jun 25; 9(6). PMID: 32575504    Free PMC article.
Severely ill COVID-19 patients display augmented functional properties in SARS-CoV-2-reactive CD8 + T cells.
Anthony Kusnadi, Ciro Ramírez-Suástegui, +8 authors, Christian H Ottensmeier.
bioRxiv, 2020 Jul 18;. PMID: 32676602    Free PMC article.
IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy.
Ting Zhou, William Damsky, +10 authors, Aaron M Ring.
Nature, 2020 Jun 26; 583(7817). PMID: 32581358    Free PMC article.
Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure.
Selena Vigano, Sara Bobisse, +2 authors, Alexandre Harari.
Front Immunol, 2020 Jul 28; 11. PMID: 32714330    Free PMC article.
Review.
Mechanisms of JAK-STAT signaling pathway mediated by CXCL8 gene silencing on epithelial-mesenchymal transition of human cutaneous melanoma cells.
Xiaorui Hu, Lili Yuan, Teng Ma.
Oncol Lett, 2020 Jul 30; 20(2). PMID: 32724443    Free PMC article.
Modulation of Determinant Factors to Improve Therapeutic Combinations with Immune Checkpoint Inhibitors.
Magalie Dosset, Elodie Lauret-Marie Joseph, Thaiz Rivera Vargas, Lionel Apetoh.
Cells, 2020 Jul 28; 9(7). PMID: 32707692    Free PMC article.
Review.
CD8+ T cells located in tertiary lymphoid structures are associated with improved prognosis in patients with gastric cancer.
Qing Li, Dachuan Zhang, +8 authors, Jingting Jiang.
Oncol Lett, 2020 Aug 13; 20(3). PMID: 32782582    Free PMC article.
CD8+ T cell states in human cancer: insights from single-cell analysis.
Anne M van der Leun, Daniela S Thommen, Ton N Schumacher.
Nat Rev Cancer, 2020 Feb 07; 20(4). PMID: 32024970    Free PMC article.
Review.
Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis.
Chisom Ifeoma Adaeze Okwor, Jun Seok Oh, +2 authors, Seung-Hwan Lee.
iScience, 2020 Sep 14; 23(9). PMID: 32920488    Free PMC article.
TCR sequencing paired with massively parallel 3' RNA-seq reveals clonotypic T cell signatures.
Ang A Tu, Todd M Gierahn, +6 authors, J Christopher Love.
Nat Immunol, 2019 Nov 21; 20(12). PMID: 31745340    Free PMC article.
Tumor-infiltrating TNFRSF9+ CD8+ T cells define different subsets of clear cell renal cell carcinoma with prognosis and immunotherapeutic response.
Yaohui Li, Zewei Wang, +15 authors, Jiejie Xu.
Oncoimmunology, 2020 Nov 13; 9(1). PMID: 33178496    Free PMC article.
Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation.
Zilei Liu, Jie P Li, +5 authors, Peng Wu.
Cell, 2020 Oct 24; 183(4). PMID: 33096019    Free PMC article.
Analysis of tumor-infiltrating NK and T cells highlights IL-15 stimulation and TIGIT blockade as a combination immunotherapy strategy for soft tissue sarcomas.
Sean J Judge, Morgan A Darrow, +14 authors, Robert J Canter.
J Immunother Cancer, 2020 Nov 08; 8(2). PMID: 33158916    Free PMC article.
Endogenous Glucocorticoid Signaling Regulates CD8+ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment.
Nandini Acharya, Asaf Madi, +17 authors, Ana C Anderson.
Immunity, 2020 Sep 17; 53(3). PMID: 32937153    Free PMC article.
Re-programming immunosurveillance in persistent non-infectious ocular inflammation.
Simon J Epps, Joanne Boldison, +5 authors, Lindsay B Nicholson.
Prog Retin Eye Res, 2018 Mar 14; 65. PMID: 29530739    Free PMC article.
Review.
Systems Immunology: Learning the Rules of the Immune System.
Alexandra-Chloé Villani, Siranush Sarkizova, Nir Hacohen.
Annu Rev Immunol, 2018 Apr 21; 36. PMID: 29677477    Free PMC article.
Review.
Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade.
Brian C Miller, Debattama R Sen, +24 authors, W Nicholas Haining.
Nat Immunol, 2019 Feb 20; 20(3). PMID: 30778252    Free PMC article.
Highly Cited.
CRISPR-Based Editing Techniques for Genetic Manipulation of Primary T Cells.
Mateusz Kotowski, Sumana Sharma.
Methods Protoc, 2020 Nov 22; 3(4). PMID: 33217926    Free PMC article.
Review.
T Cell Dysfunction in Cancer.
Daniela S Thommen, Ton N Schumacher.
Cancer Cell, 2018 Apr 11; 33(4). PMID: 29634943    Free PMC article.
Highly Cited. Review.
4-1BB co-stimulation further enhances anti-PD-1-mediated reinvigoration of exhausted CD39+ CD8 T cells from primary and metastatic sites of epithelial ovarian cancers.
Galam Leem, Junsik Park, +12 authors, Su-Hyung Park.
J Immunother Cancer, 2020 Dec 19; 8(2). PMID: 33335029    Free PMC article.
Deletion of Cbl-b inhibits CD8+ T-cell exhaustion and promotes CAR T-cell function.
Jitendra Kumar, Ritesh Kumar, +6 authors, K Venuprasad.
J Immunother Cancer, 2021 Jan 20; 9(1). PMID: 33462140    Free PMC article.
Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid.
Michael Heming, Xiaolin Li, +15 authors, Gerd Meyer Zu Hörste.
Immunity, 2021 Jan 01; 54(1). PMID: 33382973    Free PMC article.
PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19.
Min-Seok Rha, Hye Won Jeong, +22 authors, Eui-Cheol Shin.
Immunity, 2020 Dec 19; 54(1). PMID: 33338412    Free PMC article.
Control of chronic lymphocytic leukemia development by clonally-expanded CD8+ T-cells that undergo functional exhaustion in secondary lymphoid tissues.
Bola S Hanna, Philipp M Roessner, +9 authors, Martina Seiffert.
Leukemia, 2018 Sep 30; 33(3). PMID: 30267008
BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8+ T cells.
Chen Yao, Guohua Lou, +19 authors, Tuoqi Wu.
Nat Immunol, 2021 Feb 13; 22(3). PMID: 33574619    Free PMC article.
Metabolic and epigenetic regulation of T-cell exhaustion.
Fabien Franco, Alison Jaccard, +2 authors, Ping-Chih Ho.
Nat Metab, 2020 Sep 23; 2(10). PMID: 32958939
Review.
Using CRISPR to enhance T cell effector function for therapeutic applications.
Julian J Freen-van Heeren.
Cytokine X, 2021 Feb 20; 3(1). PMID: 33604565    Free PMC article.
Review.
Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy.
Weiqin Jiang, Yinjun He, +9 authors, Hanju Hua.
Front Immunol, 2021 Feb 27; 11. PMID: 33633741    Free PMC article.
Review.
A road map from single-cell transcriptome to patient classification for the immune response to trauma.
Tianmeng Chen, Matthew J Delano, +13 authors, Timothy R Billiar.
JCI Insight, 2020 Dec 16; 6(2). PMID: 33320841    Free PMC article.
Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment.
Kristen E Pauken, Osmaan Shahid, +18 authors, Meromit Singer.
J Exp Med, 2021 Mar 03; 218(4). PMID: 33651880    Free PMC article.
Proteomics of Melanoma Response to Immunotherapy Reveals Mitochondrial Dependence.
Michal Harel, Rona Ortenberg, +23 authors, Tamar Geiger.
Cell, 2019 Sep 10; 179(1). PMID: 31495571    Free PMC article.
Rethinking peripheral T cell tolerance: checkpoints across a T cell's journey.
Mohamed A ElTanbouly, Randolph J Noelle.
Nat Rev Immunol, 2020 Oct 21; 21(4). PMID: 33077935
Review.
Decoding Cancer Biology One Cell at a Time.
L Nicolas Gonzalez Castro, Itay Tirosh, Mario L Suvà.
Cancer Discov, 2021 Apr 04; 11(4). PMID: 33811126    Free PMC article.
Review.
Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39.
Maisa C Takenaka, Galina Gabriely, +24 authors, Francisco J Quintana.
Nat Neurosci, 2019 Apr 10; 22(5). PMID: 30962630    Free PMC article.
Highly Cited.
In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer.
Zeyu Chen, Eri Arai, +25 authors, Junwei Shi.
Cell, 2021 Feb 27; 184(5). PMID: 33636129    Free PMC article.
CD8+ T Cell Priming in Established Chronic Viral Infection Preferentially Directs Differentiation of Memory-like Cells for Sustained Immunity.
Laura M Snell, Bethany L MacLeod, +8 authors, David G Brooks.
Immunity, 2018 Oct 14; 49(4). PMID: 30314757    Free PMC article.
The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy.
Saeed Asiry, Gina Kim, +5 authors, George S Karagiannis.
Front Immunol, 2021 May 01; 12. PMID: 33927723    Free PMC article.
Review.
Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells.
Anthony Kusnadi, Ciro Ramírez-Suástegui, +8 authors, Christian H Ottensmeier.
Sci Immunol, 2021 Jan 23; 6(55). PMID: 33478949    Free PMC article.
Tim-3 adaptor protein Bat3 is a molecular checkpoint of T cell terminal differentiation and exhaustion.
Chen Zhu, Karen O Dixon, +15 authors, Vijay Kuchroo.
Sci Adv, 2021 May 02; 7(18). PMID: 33931442    Free PMC article.
Interpretation of T cell states from single-cell transcriptomics data using reference atlases.
Massimo Andreatta, Jesus Corria-Osorio, +3 authors, Santiago J Carmona.
Nat Commun, 2021 May 22; 12(1). PMID: 34017005    Free PMC article.
Progressive immune dysfunction with advancing disease stage in renal cell carcinoma.
David A Braun, Kelly Street, +32 authors, Catherine J Wu.
Cancer Cell, 2021 Mar 13; 39(5). PMID: 33711273    Free PMC article.
Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer.
Jieti Wang, Ruochen Li, +12 authors, Hua Huang.
Nat Commun, 2021 May 27; 12(1). PMID: 34035252    Free PMC article.
Global Gene Expression of T Cells Is Differentially Regulated by Peritoneal Dendritic Cell Subsets in an IL-2 Dependent Manner.
Moah Sohn, Hye Young Na, +8 authors, Chae Gyu Park.
Front Immunol, 2021 Jun 04; 12. PMID: 34079542    Free PMC article.
CRISPR/Cas9 Gene-Editing in Cancer Immunotherapy: Promoting the Present Revolution in Cancer Therapy and Exploring More.
Xuejin Ou, Qizhi Ma, +2 authors, Zhiyao He.
Front Cell Dev Biol, 2021 Jun 08; 9. PMID: 34095145    Free PMC article.
Review.
Type 17 immunity promotes the exhaustion of CD8+ T cells in cancer.
Byung-Seok Kim, Da-Sol Kuen, +15 authors, Yeonseok Chung.
J Immunother Cancer, 2021 Jun 05; 9(6). PMID: 34083422    Free PMC article.
A cellular and spatial map of the choroid plexus across brain ventricles and ages.
Neil Dani, Rebecca H Herbst, +19 authors, Maria K Lehtinen.
Cell, 2021 May 02; 184(11). PMID: 33932339    Free PMC article.
Phenotypes and Functions of SARS-CoV-2-Reactive T Cells.
Min Kyung Jung, Eui-Cheol Shin.
Mol Cells, 2021 Jun 15; 44(6). PMID: 34120892    Free PMC article.
Review.
CD8+ T cell differentiation and dysfunction in cancer.
Mary Philip, Andrea Schietinger.
Nat Rev Immunol, 2021 Jul 14; 22(4). PMID: 34253904
Review.
Type 1 conventional dendritic cells and interferons are required for spontaneous CD4+ and CD8+ T-cell protective responses to breast cancer.
Raphaël Mattiuz, Carine Brousse, +9 authors, Karine Crozat.
Clin Transl Immunology, 2021 Jul 20; 10(7). PMID: 34277006    Free PMC article.
CD147 regulates antitumor CD8+ T-cell responses to facilitate tumor-immune escape.
Yatong Chen, Jing Xu, +10 authors, Zhi-Nan Chen.
Cell Mol Immunol, 2020 Nov 13; 18(8). PMID: 33177695    Free PMC article.
Dendritic cells in tumor microenvironment promoted the neuropathic pain via paracrine inflammatory and growth factors.
Zhun Wang, Kai Song, Wenxin Zhao, Zhongmin Zhao.
Bioengineered, 2020 May 22; 11(1). PMID: 32434423    Free PMC article.
Dynamic chromatin regulatory landscape of human CAR T cell exhaustion.
David G Gennert, Rachel C Lynn, +10 authors, Howard Y Chang.
Proc Natl Acad Sci U S A, 2021 Jul 22; 118(30). PMID: 34285077    Free PMC article.
Cancer biology deciphered by single-cell transcriptomic sequencing.
Yanmeng Li, Jianshi Jin, Fan Bai.
Protein Cell, 2021 Aug 19; 13(3). PMID: 34405376    Free PMC article.
Review.
Activation or exhaustion of CD8+ T cells in patients with COVID-19.
Min-Seok Rha, Eui-Cheol Shin.
Cell Mol Immunol, 2021 Aug 21; 18(10). PMID: 34413488    Free PMC article.
Review.
CRISPR/Cas9 revitalizes adoptive T-cell therapy for cancer immunotherapy.
Sasan Ghaffari, Nastaran Khalili, Nima Rezaei.
J Exp Clin Cancer Res, 2021 Aug 28; 40(1). PMID: 34446084    Free PMC article.
Review.
Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement.
Ai Lin Chin, Shan Jiang, +4 authors, Rong Tong.
Nat Commun, 2021 Aug 28; 12(1). PMID: 34446702    Free PMC article.
IgG Immune Complexes Inhibit Naïve T Cell Proliferation and Suppress Effector Function in Cytotoxic T Cells.
Wissam Charab, Matthew G Rosenberger, +8 authors, George Georgiou.
Front Immunol, 2021 Aug 28; 12. PMID: 34447380    Free PMC article.
CD8+ Regulatory T Cell - A Mystery to Be Revealed.
Shruti Mishra, Saranya Srinivasan, Chaoyu Ma, Nu Zhang.
Front Immunol, 2021 Sep 07; 12. PMID: 34484208    Free PMC article.
Review.
A Cancer-Selective Zinc Ionophore Inspired by the Natural Product Naamidine A.
Rachel M Vaden, Katrin P Guillen, +7 authors, Bryan E Welm.
ACS Chem Biol, 2018 Dec 21; 14(1). PMID: 30571086    Free PMC article.
The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer.
William A Freed-Pastor, Laurens J Lambert, +21 authors, Tyler Jacks.
Cancer Cell, 2021 Aug 07; 39(10). PMID: 34358448    Free PMC article.
Cyclophosphamide enhances the antitumor potency of GITR engagement by increasing oligoclonal cytotoxic T cell fitness.
Daniel Hirschhorn, Allison Betof Warner, +11 authors, Jedd D Wolchok.
JCI Insight, 2021 Oct 23; 6(20). PMID: 34676831    Free PMC article.
Alteration of the Immune Microenvironment in HBsAg and HBeAg Dual-Positive Pregnant Women Presenting a High HBV Viral Load.
Fan Gao, Hongyan Wang, +5 authors, Guiqin Bai.
J Inflamm Res, 2021 Nov 13; 14. PMID: 34764667    Free PMC article.
A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing antitumor immune response.
Kelli A Connolly, Manik Kuchroo, +19 authors, Nikhil S Joshi.
Sci Immunol, 2021 Oct 02; 6(64). PMID: 34597124    Free PMC article.
Single-cell normalization and association testing unifying CRISPR screen and gene co-expression analyses with Normalisr.
Lingfei Wang.
Nat Commun, 2021 Nov 06; 12(1). PMID: 34737291    Free PMC article.
Antigen and checkpoint receptor engagement recalibrates T cell receptor signal strength.
Thomas A E Elliot, Emma K Jennings, +6 authors, David Bending.
Immunity, 2021 Sep 18; 54(11). PMID: 34534438    Free PMC article.
Strong Expansion of Human Regulatory T Cells for Adoptive Cell Therapy Results in Epigenetic Changes Which May Impact Their Survival and Function.
Kristy Ou, Dania Hamo, +13 authors, Julia K Polansky.
Front Cell Dev Biol, 2021 Dec 07; 9. PMID: 34869339    Free PMC article.
Characterization of the GATA Transcription Factor Family and Exploration of Their Relevance to Immune Infiltration and Tumor Microenvironment in Pancreatic Cancer.
Jiaqi Xu, Kun Cheng, +7 authors, Qilong Chen.
Int J Gen Med, 2021 Dec 09; 14. PMID: 34876843    Free PMC article.
Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer.
Hui Peng, C Alston James, +11 authors, William G Hawkins.
Clin Cancer Res, 2021 Oct 02; 27(24). PMID: 34593529    Free PMC article.
Combinatorial immunotherapy induces tumor-infiltrating CD8+ T cells with distinct functional, migratory, and stem-like properties.
Natalija Van Braeckel-Budimir, Joseph Samuel Dolina, +14 authors, Shahram Salek-Ardakani.
J Immunother Cancer, 2021 Dec 15; 9(12). PMID: 34903555    Free PMC article.
Divergent fates of antigen-specific CD8+ T cell clones in mice with acute leukemia.
Xiufen Chen, Brendan W MacNabb, +2 authors, Justin Kline.
Cell Rep, 2021 Nov 11; 37(6). PMID: 34758311    Free PMC article.
An NK-like CAR T cell transition in CAR T cell dysfunction.
Charly R Good, M Angela Aznar, +27 authors, Carl H June.
Cell, 2021 Dec 04; 184(25). PMID: 34861191    Free PMC article.
T cell responses to SARS-CoV-2 in humans and animals.
Sameer-Ul-Salam Mattoo, Jinjong Myoung.
J Microbiol, 2022 Feb 15; 60(3). PMID: 35157219    Free PMC article.
Review.
T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10.
Vidhya M Ravi, Nicolas Neidert, +25 authors, Dieter Henrik Heiland.
Nat Commun, 2022 Feb 19; 13(1). PMID: 35177622    Free PMC article.
29 m6A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation - 102 Transcriptomic Dataset Analyses.
Ming Liu, Keman Xu, +14 authors, Xiaofeng Yang.
J Immunol Res, 2022 Feb 26; 2022. PMID: 35211628    Free PMC article.
A genome-scale screen for synthetic drivers of T cell proliferation.
Mateusz Legut, Zoran Gajic, +11 authors, Neville E Sanjana.
Nature, 2022 Mar 18; 603(7902). PMID: 35296855
Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma.
Maria A Garcia-Marquez, Martin Thelen, +14 authors, Hans A Schlößer.
Leukemia, 2021 Sep 30; 36(3). PMID: 34584203    Free PMC article.
Molecular and Functional Signatures Associated with CAR T Cell Exhaustion and Impaired Clinical Response in Patients with B Cell Malignancies.
Katia Beider, Orit Itzhaki, +13 authors, Michal J Besser.
Cells, 2022 Apr 13; 11(7). PMID: 35406703    Free PMC article.
Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy.
Pavan Bachireddy, Elham Azizi, +19 authors, Catherine J Wu.
Cell Rep, 2021 Nov 11; 37(6). PMID: 34758319    Free PMC article.
Heterogeneity and clonality of kidney-infiltrating T cells in murine lupus nephritis.
Shuchi Smita, Maria Chikina, Mark J Shlomchik, Jeremy S Tilstra.
JCI Insight, 2022 Mar 11; 7(8). PMID: 35271505    Free PMC article.
In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue.
Zhi Li, Zewen K Tuong, +16 authors, David R Withers.
J Exp Med, 2022 Apr 27; 219(6). PMID: 35472220    Free PMC article.
An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes.
Abhinav Jaiswal, Akanksha Verma, +17 authors, Niroshana Anandasabapathy.
Cancer Cell, 2022 May 11; 40(5). PMID: 35537413    Free PMC article.
Epigenetic regulation of T cell exhaustion.
Julia A Belk, Bence Daniel, Ansuman T Satpathy.
Nat Immunol, 2022 May 28; 23(6). PMID: 35624210
Review.