Loss of Tapasin in Tumors Potentiates T-Cell Recognition and Anti-Tumor Effects of Immune Checkpoint Blockade.

ABSTRACT: Tumors can evade host immune surveillance by compromising the intracellular antigen processing machinery (APM), such as beta 2 macroglobulin (β2m) or the transporter associated with antigen processing (TAP). Defects in the APM generally result in the downregulation of surface MHC class I (MHC-I) levels. Here, we show that the downregulation of a component of the peptide loading complex (PLC), tapasin, in tumors conversely induces CD8⁺ T-cell responses and inhibits tumor growth in vivo. Loss of tapasin enhanced the anti-tumor effects of immune checkpoint blockade (ICB) in mouse non-small cell lung and colon cancer models. In contrast to β2m-deficient tumors, the reduced levels of MHC-I in tapasin-deficient tumors were restored by IFN-γ treatment, allowing them to be recognized by

SUBMITTER: Moniwa K 

PROVIDER: S-EPMC12044650 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature