Unknown

Dataset Information

0

Intratumoral CD4+ T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer.


ABSTRACT: 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 repertoires of CD8+ T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4+ T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4+ T cell states that are clonally expanded. These CD4+ T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, 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.

SUBMITTER: Oh DY 

PROVIDER: S-EPMC7321885 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

2020-06-01 | GSE149652 | GEO
| PRJNA629542 | ENA
| S-EPMC6435583 | biostudies-literature
| S-EPMC5048774 | biostudies-literature
| S-EPMC9037432 | biostudies-literature
| S-EPMC7909889 | biostudies-literature
| S-EPMC8783893 | biostudies-literature
| S-EPMC10699039 | biostudies-literature
| S-EPMC7354862 | biostudies-literature
| S-EPMC8423719 | biostudies-literature