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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

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

Project description: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 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 tumor 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.

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

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

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TLR3 Activation of Intratumoral CD103+ Dendritic Cells Modifies the Tumor Infiltrate Conferring Anti-tumor Immunity.

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