PD-L1+ exosomes from bone marrow-derived cells of tumor-bearing mice inhibit antitumor immunity

Abstract

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.