High-dimensional single cell analysis identifies stem-like cytotoxic CD8+ T cells infiltrating human tumors

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.

Source: The Journal of Experimental Medicine - October 1, 2018 Category: Internal Medicine Authors: Brummelman, J., Mazza, E. M. C., Alvisi, G., Colombo, F. S., Grilli, A., Mikulak, J., Mavilio, D., Alloisio, M., Ferrari, F., Lopci, E., Novellis, P., Veronesi, G., Lugli, E. Tags: Solid Tumors, Tumor Immunology Articles Source Type: research