The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival

被引:107
作者
Valpione, Sara [1 ]
Mundra, Piyushkumar A. [1 ]
Galvani, Elena [1 ]
Campana, Luca G. [2 ,3 ]
Lorigan, Paul [2 ]
De Rosa, Francesco [4 ]
Gupta, Avinash [2 ]
Weightman, John [5 ]
Mills, Sarah [6 ]
Dhomen, Nathalie [1 ]
Marais, Richard [1 ]
机构
[1] Univ Manchester, Canc Res UK Manchester Inst, Mol Oncol Grp, Alderley Pk, Macclesfield, Cheshire, England
[2] Christie NHS Fdn Trust, Med Oncol, Manchester, Lancs, England
[3] Univ Padua, Dept Surg Oncol & Gastroenterol Sci DISCOG, Dept Surg, Christie NHS Fdn Trust, Manchester, Lancs, England
[4] Ist Sci Romagnolo & Cura Tumori IRST Dino Amadori, Immunotherapy Cell Therapy & Biobank, Meldola, Italy
[5] Univ Manchester, Canc Res UK Manchester Inst, Mol Biol Core Facil, Alderley Pk, Macclesfield, Cheshire, England
[6] Christie NHS Fdn Trust, Manchester Canc Res Ctr Biobank, Manchester, Lancs, England
基金
英国惠康基金;
关键词
D O I
10.1038/s41467-021-24343-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes could therefore be indicative of the functional state of these cells and determine disease course at different stages in cancer progression. Here we show that the diversity of the TCR of tumor infiltrating T cell at baseline is prognostic in various cancers, whereas the TCR clonality of T cell infiltrating metastatic melanoma pre-treatment is predictive for activity and efficacy of PD1 blockade immunotherapy. Precision medicine needs prognostic markers to select the patients that will benefit more from targeted therapy. Authors show here that high level of baseline T cell receptor diversity is an indicator of favourable prognosis in multiple cancer types, and monoclonal expansion of T-cells correlates with good response to immune checkpoint blockade therapy in metastatic melanoma patients.
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页数:8
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