PDL1-positive exosomes suppress antitumor immunity by inducing tumor-specific CD8⁺ T cell exhaustion during metastasis.

ABSTRACT: Metastasis is the main cause of death in individuals with cancer. Immune checkpoint blockade (ICB) can potentially reverse CD8⁺ cytotoxic T lymphocytes (CTLs) dysfunction, leading to significant remission in multiple cancers. However, the mechanism underlying the development of CTL exhaustion during metastatic progression remains unclear. Here, we established an experimental pulmonary metastasis model with melanoma cells and discovered a critical role for melanoma-released exosomes in metastasis. Using genetic knockdown of nSMase2 and Rab27a, 2 key enzymes for exosome secretion, we showed that high levels of effector-like tumor-specific CD8⁺ T cells with transitory exhaustion, instead of terminal exhaustion, were observed in mice without exosomes; these cells showed l

SUBMITTER: Chen J 

PROVIDER: S-EPMC8409314 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature