Tumors escape immune attack by upregulating the surface expression of PD-L1, which interacts with PD-1 on T cells to activate immune inhibitory signaling. Anti-PD-1 treatments can effectively block this inhibitory signaling and activate antitumor immune responses. However, anti-PD-1 treatment also has a tumor suppressive effect in patients whose tumor cells do not express PD-L1. The underlying mechanisms are poorly defined. Here, we report that exosomes from bone marrow-derived cells (BMDCs) in tumor-bearing mice, but not in healthy mice, carry PD-L1. PD-L1 on these exosomes is biofunctional and can inhibit CD8⁺ T cell proliferation and activation in vitro and in vivo. The transfer of exogenous exosomes from BMDCs and the inhibition of the production of endogenous exosomes by BMDCs promote and suppress tumor growth, respectively. PD-L1⁺ exosomes from BMDCs can be found in tumor tissues. In addition, exosomes from BMDCs promote tumor metastasis in a PD-L1-dependent manner. Therefore, our results indicate that exosomes from BMDCs play important roles in tumor immunosuppression via PD-L1.

肿瘤通过上调 PD-L1 的表面表达来逃避免疫攻击，PD-L1 与 T 细胞上的 PD-1 相互作用以激活免疫抑制信号。抗 PD-1 治疗可以有效阻断这种抑制性信号并激活抗肿瘤免疫反应。然而，抗 PD-1 治疗对肿瘤细胞不表达 PD-L1 的患者也有抑癌作用。基本机制定义不明确。在这里，我们报告了来自荷瘤小鼠的骨髓衍生细胞 (BMDCs) 的外泌体携带 PD-L1，而健康小鼠则没有。这些外泌体上的 PD-L1 具有生物功能，可以抑制 CD8 ⁺T细胞在体外和体内的增殖和活化。从BMDCs转移外源性外泌体和抑制BMDCs产生内源性外泌体分别促进和抑制肿瘤生长。来自 BMDCs的 PD-L1 ⁺外泌体可以在肿瘤组织中找到。此外，来自 BMDCs 的外泌体以 PD-L1 依赖性方式促进肿瘤转移。因此，我们的结果表明来自 BMDCs 的外泌体通过 PD-L1 在肿瘤免疫抑制中发挥重要作用。