CD8⁺ T cells maintain killing of MHC-I-negative tumor cells through the NKG2D-NKG2DL axis.

ABSTRACT: The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8⁺ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, we report that CD8⁺ T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression. This capacity proves to be dependent instead on interactions between T cell natural killer group 2D (NKG2D) and tumor NKG2D ligands (NKG2DLs), the latter of which are highly expressed on MHC-loss variants. Necessarily, tumor cell killing in these instances is antigen independent, although prior T cell antigen-s

SUBMITTER: Lerner EC 

PROVIDER: S-EPMC10518253 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature