Department of Infectious Disease, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, 310052, Hangzhou, China.
Department of Comprehensive Medical Oncology, Zhejiang Cancer Hospital, 310022, Hangzhou, China.
Cell Mol Immunol. 2021 Oct;18(10):2402-2409. doi: 10.1038/s41423-020-0487-7. Epub 2020 Jun 30.
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，激活免疫抑制信号。抗 PD-1 治疗可以有效地阻断这种抑制性信号，激活抗肿瘤免疫反应。然而，抗 PD-1 治疗在肿瘤细胞不表达 PD-L1 的患者中也具有肿瘤抑制作用。其潜在机制尚未明确。在这里，我们报告称，荷瘤小鼠骨髓来源细胞（BMDC）来源的外泌体携带 PD-L1，但健康小鼠的外泌体不携带 PD-L1。这些外泌体上的 PD-L1 具有生物功能，可在体外和体内抑制 CD8 T 细胞的增殖和激活。外源性 BMDC 来源的外泌体的转移和 BMDC 内源性外泌体产生的抑制分别促进和抑制肿瘤生长。可以在肿瘤组织中发现 BMDC 来源的 PD-L1 外泌体。此外，BMDC 来源的外泌体以 PD-L1 依赖的方式促进肿瘤转移。因此，我们的结果表明，BMDC 来源的外泌体通过 PD-L1 在肿瘤免疫抑制中发挥重要作用。
