Qa-1^b Modulates Resistance to Anti-PD-1 Immune Checkpoint Blockade in Tumors with Defects in Antigen Processing.

ABSTRACT: Immune checkpoint blockade (ICB) has improved cancer care, but ICB is only effective in some patients. The molecular mechanisms that influence ICB therapy response are not completely understood. The non-classical MHC class I molecule HLA-E and its mouse ortholog, Qa-1^b, present a limited set of peptides in a TAP1-dependent manner to the NKG2A/CD94 heterodimer to transduce an inhibitory signal to natural killer (NK) and CD8⁺ T cells. However, deficiency of TAP1 allows Qa-1^b to present an alternative peptidome to Qa-1^b-restricted T-cell receptors of cytotoxic T cells. In this study, we used CRISPR-Cas9 to study the relationship between TAP1, Qa-1^b, and response to anti-PD1 therapy. We hypothesized that immunotherapy response in TAP1-defi

SUBMITTER: Zhang X 

PROVIDER: S-EPMC8178214 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature