Abstract
Cancer cells escape immune surveillance by suppressing immune responses through the binding of Programmed cell Death-Ligand 1 (PD-L1), which is abundantly expressed on the cell surface, to PD-1 on the surface of T cells. The regulation of cell surface PD-L1, one of these immune checkpoint molecules, is extremely important because it is a target for cancer immunotherapy; however, the intracellular trafficking pathway of PD-L1 has not been fully elucidated. Recently, we reported that Rab10, a small GTPase, localizes to a novel tubular endocytic pathway that evades the lysosomal degradation system. In this study, using live cells expressing GFP-PD-L1 and mScarlet-Rab10, we revealed that PD-L1 localizes in Rab10-positive endocytic tubules in some types of cancer cells. Typically, in HeLaM cells, Rab10-positive tubular structures of which membranes have PD-L1 extend from the plasma membrane toward the cell-central region. However, in Rab10-knockout HeLaM cells, no PD-L1-localized tubular structures were observed. We also found that PD-L1 dimerized by the PD-L1 inhibitor BMS-202 was removed from the cell surface and Rab10-positive tubular endosomes and transported to the lysosomal degradation system. Taken together, this study provides novel insights that the Rab10-dependent tubular endocytic pathway may play an important role in the intracellular reservoir and recycling of PD-L1 to the surface of cancer cells, possibly regulating the amount of PD-L1 on the cell surface.