γδ T cells are effectors of immunotherapy in cancers with HLA class I defects.

ABSTRACT: DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB)^1,2. Here, in contrast to other cancer types^3-5, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8⁺ T cells in this context. We next identified a strong association between B2M inactivation and increased infiltration by γδ T cells in MMR-d cancers. These γδ T cells mainly comprised the Vδ1 and Vδ3 subsets, and expressed high levels of PD-1, other activation markers, including cytotoxic molecules, and a broad repertoire of ki

SUBMITTER: de Vries NL 

PROVIDER: S-EPMC9876799 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature