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Brummelman, Jolanda; Mazza, Emilia M C; Alvisi, Giorgia; Colombo, Federico S; Grilli, Andrea; Mikulak, Joanna; Mavilio, Domenico; Alloisio, Marco; Ferrari, Francesco; Lopci, Egesta; Novellis, Pierluigi; Veronesi, Giulia; Lugli, Enrico
The Journal of experimental medicine, 2018-Oct-01, 2018-10-01, 20181001, Letnik: 215, Številka: 10Journal Article
CD8 T cells infiltrating tumors are largely dysfunctional, but whether a subset maintains superior functionality remains ill defined. By high-dimensional single cell analysis of millions of CD8 T cells from 53 individuals with lung cancer, we defined those subsets that are enriched in tumors compared with cancer-free tissues and blood. Besides exhausted and activated cells, we identified CXCR5 TIM-3 CD8 T cells with a partial exhausted phenotype, while retaining gene networks responsible for stem-like plasticity and cytotoxicity, as revealed by single cell sequencing of the whole transcriptome. Ex vivo, CXCR5 TIM-3 CD8 T cells displayed enhanced self-renewal and multipotency compared with more differentiated subsets and were largely polyfunctional. Analysis of inhibitory and costimulatory receptors revealed PD-1, TIGIT, and CD27 as possible targets of immunotherapy. We thus demonstrate a hierarchy of differentiation in the context of T cell exhaustion in human cancer similar to that of chronically infected mice, which is further shown to disappear with disease progression.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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