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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\u2010released exosomes in metastasis. Using genetic knockdown of <jats:italic>nSMase2<\/jats:italic> and <jats:italic>Rab27a<\/jats:italic>, 2 key enzymes for exosome secretion, we showed that high levels of effector\u2010like tumor\u2010specific CD8<jats:sup>+<\/jats:sup> T cells with transitory exhaustion, instead of terminal exhaustion, were observed in mice without exosomes; these cells showed limited inhibitory receptors and strong proliferation and cytotoxicity. Mechanistically, the immunosuppression of exosomes depends on exogenous PD\u2010L1, which can be largely rescued by pretreatment with antibody blockade. Notably, we also found that exosomal PD\u2010L1 acts as a promising predictive biomarker for ICB therapies during metastasis. Together, our findings suggest that exosomal PD\u2010L1 may be a potential immunotherapy target, suggesting a new curative therapy for tumor metastasis.<\/jats:p>","DOI":"10.1111\/cas.15033","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T13:03:21Z","timestamp":1624280601000},"page":"3437-3454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["PDL1\u2010positive exosomes suppress antitumor immunity by inducing tumor\u2010specific CD8<sup>+<\/sup> T cell exhaustion during metastasis"],"prefix":"10.1111","volume":"112","author":[{"given":"Ji","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Huashan Hospital Fudan University 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