B2-Microglobulin

Checkpoint inhibitor resistance, which ultimately leads to resistance to therapy, may be attributed to the absence of tumor antigens or that the tumor antigen is not presenting on the tumor surface due to alterations of beta-2 microglobulin (B2M) or MHC. B2M is required for MHCI folding and transport to the cell surface. Loss of B2M leads to a lack of CD8+ T-cell recognition and also loss of MHCI. This mechanism of acquired resistance has been documented in the resistance to anti-PD-1 therapy, where mutations in B2M lead to a lack of surface expression of MHCI.