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

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 CD8(+) T cells. These results suggest the presence of a reactive CD8(+) T-cell fraction and the ability of immune surveillance to eliminate tumor variants with impaired tapasin expression.