Intratumoral CD4+ T cells mediate anti-tumor cytotoxicity in human bladder cancer

By D. Oh, S. Kwek, Siddharth S. Raju, Tony Li, Elizabeth McCarthy, E. Chow, D. Aran, A. Ilano, C. Pai, Chiara Rancan and 10 more. Cell, 2020

604 citations recorded by the source corpus.

Summary Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoire of CD8+ T cells are not altered in tumors compared to non-malignant tissues. In contrast, single-cell analysis of CD4+ T cells demonstrate several tumor-specific states including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4+ T cell states, which are clonally expanded. These CD4+ T cells can kill autologous tumor in an MHC class II dependent fashion and are suppressed by the regulatory T cells. Further, a gene signature of cytotoxic CD4+ T cells in tumors predicts clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.

Subfields: Immunology, Oncology, Surgery

View Paper: https://www.semanticscholar.org/paper/e52ca58b09057c7b922b66ae013add720559b182