PD-1 suppresses the maintenance of cell couples between cytotoxic T cells and target tumor cells within the tumor.

ABSTRACT: The killing of tumor cells by CD8⁺ T cells is suppressed by the tumor microenvironment, and increased expression of inhibitory receptors, including programmed cell death protein-1 (PD-1), is associated with tumor-mediated suppression of T cells. To find cellular defects triggered by tumor exposure and associated PD-1 signaling, we established an ex vivo imaging approach to investigate the response of antigen-specific, activated effector CD8⁺ tumor-infiltrating lymphocytes (TILs) after interaction with target tumor cells. Although TIL-tumor cell couples readily formed, couple stability deteriorated within minutes. This was associated with impaired F-actin clearing from the center of the cellular interface, reduced Ca²⁺ signaling, increased TIL locomotion, an

SUBMITTER: Ambler R 

PROVIDER: S-EPMC7784968 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature