Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis.

The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) axis mediates immune evasion of tumor, and targeting this axis has achieved some clinical benefits. The regulation of PD-1 expression in immune cells has been well studied. However, whether any other potential source of immune cell-expressed PD-1 exists remains unknown. Here, we report that tumor cells express PD-1 and release PD-1 in the form of extracellular vesicles, which enters T cells and suppresses T cell function via PD-L1 in vitro. In vivo, tumor cell-derived extracellular vesicle PD-1 promotes tumor growth via disrupting peripheral T cell homeostasis, showing by decreased number of T cells and impaired function of CD8 T cells in spleens, draining lymph nodes and tumor infiltrating lymphocytes, which is restored by PD-1-targeted antibodies. Our study provides a unique and novel perspective for immune evasion of tumor, and expands a source of PD-1 in immune cells.