Project description:Follicular regulatory T cells (TFR cells) and their functional role in cancer have been completely disregarded so far. Our data identify that as a critical oversight, as these cells account for a substantial proportion of tumor-infiltrating CD4+ T cells

2022-06-01 | GSE145691 | GEO

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy [mouse]

2021-05-03 | GSE132296 | GEO

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy [human]

2021-05-03 | GSE132295 | GEO

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-05-03 | GSE132297 | GEO

Tumor-Induced Erythroid Precursor-Differentiated Myeloid Cells Mediate Immunosuppression and Curtail Anti-PD-1/PD-L1 Treatment Efficacy

Project description:Tumor-Induced Erythroid Precursor-Differentiated Myeloid Cells Mediate Immunosuppression and Curtail Anti-PD-1/PD-L1 Treatment Efficacy

| PRJNA832746 | ENA

The efficacy of chemotherapy is limited by intratumoral senescent cells that persist through the upregulation of PD-L2

Project description:Anti-cancer therapies often result in a subset of surviving cancer cells that undergo therapy induced senescence (TIS). Senescent cancer cells strongly modify the intratumoral microenvironment favoring immunosuppression and, thereby, tumor growth. An emerging strategy to optimise current therapies is to combine them with treatments that eliminate senescent cells. To this end, we undertook an unbiased proteomics approach to identify surface markers contributing to senescent cells immune evasion. Through this approach, we discovered that the immune checkpoint inhibitor PD-L2, but not PD-L1, is upregulated across multiple senescent human and murine cells. Importantly, blockade of PD-L2 strongly synergises with genotoxic chemotherapy, causing remission of solid tumors in mice. We show that PD-L2 inhibition prevents the persistence of chemotherapy-induced senescent cells, which exert cell-extrinsic immunomodulatory actions. In particular, upon chemotherapy, tumors deficient in PD-L2 fail to produce cytokines of the CXCL family, do not recruit myeloid-derived suppressor cells (MDSCs) and are eliminated in a CD8 T cell-dependent manner. We conclude that blockade of PD-L2 improves chemotherapy efficacy by reducing the intratumoral burden of senescent cells and their associated recruitment of immunosuppressive cells. These findings provide a novel strategy to exploit vulnerabilities arising in tumor cells as a result of therapy-induced damage and cellular senescence

2022-10-19 | GSE210334 | GEO