Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors
Thomas Duhen,Rebekka Duhen,Ryan Montler,Jake Moses,Tarsem Moudgil,Noel F C C de Miranda,Cheri P. Goodall,Tiffany C. Blair,Bernard A. Fox,Jason E. McDermott,Shu Ching Chang,Gary L. Grunkemeier,Rom Leidner,R.B. Bell,Andrew D. Weinberg +14 more
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TLDR
The authors show that CD39 and CD103 mark a subset of tumor-infiltrating CD8 T cells that are tumor-reactive and exhibit characteristics of exhausted or tissue-resident memory T cells, which may lead to future adoptive T-cell cancer therapies.Abstract:
Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 TILs in patients with head and neck cancer are associated with better overall survival. Our data thus describe an approach for detecting tumor-reactive CD8 TILs that will help define mechanisms of existing immunotherapy treatments, and may lead to future adoptive T-cell cancer therapies.read more
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Clonal replacement of tumor-specific T cells following PD-1 blockade.
Kathryn E. Yost,Ansuman T. Satpathy,Daniel K. Wells,Yanyan Qi,Chunlin Wang,Robin Kageyama,Katherine McNamara,Jeffrey M. Granja,Kavita Y. Sarin,Ryanne A. Brown,Rohit Gupta,Christina Curtis,Samantha L. Bucktrout,Mark M. Davis,Anne Lynn S. Chang,Howard Y. Chang +15 more
TL;DR: Paired single-cell RNA and T cell receptor sequencing on 79,046 cells from site-matched tumors from patients with basal or squamous cell carcinoma before and after anti-PD-1 therapy demonstrates that pre-existing tumor-specific T cells may have limited reinvigoration capacity, and that the T cell response to checkpoint blockade derives from a distinct repertoire of T cell clones that may have just recently entered the tumor.
Journal ArticleDOI
Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma
Hanjie Li,Anne van der Leun,Ido Yofe,Yaniv Lubling,Dikla Gelbard-Solodkin,Alexander C.J. van Akkooi,Marlous van den Braber,Elisa A. Rozeman,John B. A. G. Haanen,Christian U. Blank,Hugo M. Horlings,Eyal David,Yael Baran,Akhiad Bercovich,Aviezer Lifshitz,Ton N. Schumacher,Amos Tanay,Ido Amit +17 more
TL;DR: It is demonstrated that dysfunctional T cells are the major intratumoral proliferating immune cell compartment and that the intensity of the dysfunctional signature is associated with tumor reactivity.
Journal ArticleDOI
CD8+ T cell states in human cancer: insights from single-cell analysis
TL;DR: The CD8+ T cell states that have been identified in human tumours and the potential roles they play in tumour control as well as how they are influenced by immune checkpoint blockade are outlined.
Journal Article
Hobit and Blimp1 instruct a universal transcriptional program of tissue-residency in lymphocytes
Laura K. Mackay,Martina Minnich,Natasja A. M. Kragten,Cyril Seillet,David Freestone,Gabrielle T. Belz,Meinrad Busslinger,Wei Shi,Francis R. Carbone,R. A. W. Van Lier,Axel Kallies,K van Gisbergen +11 more
TL;DR: It is shown that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trms cells in skin, gut, liver, and kidney in mice.
Journal ArticleDOI
Intratumoral CD4+ T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer.
David Y. Oh,Serena S. Kwek,Siddharth S. Raju,Tony Li,Elizabeth E. McCarthy,Eric D. Chow,Dvir Aran,Arielle Ilano,Chien-Chun Steven Pai,Chiara Rancan,Kathryn Allaire,Arun Burra,Yang Sun,Matthew H. Spitzer,Serghei Mangul,Sima P. Porten,Maxwell V. Meng,Terence W. Friedlander,Chun Jimmie Ye,Lawrence Fong +19 more
TL;DR: A gene signature of cytotoxic CD4+ T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1, and several tumor-specific states are found, including multiple distinct states of regulatory T cells.
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TGFβ in Cancer
TL;DR: The mechanistic basis and clinical relevance of TGFbeta's role in cancer is becoming increasingly clear, paving the way for a better understanding of the complexity and therapeutic potential of this pathway.
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