Tumor cells lacking MHC class I

Tumor cells lacking MHC class I refers to a cancer cell phenotype where surface expression of major histocompatibility complex class I (MHC-I, also known as HLA class I in humans) molecules is lost or downregulated, primarily through genetic mutations (e.g., in B2M, TAP), transcriptional dysregulation (e.g., via NLRC5, IRF1), or epigenetic mechanisms. MHC-I normally presents intracellular peptides to CD8+ T cells to trigger anti-tumor immunity, but its absence allows tumors to evade T cell recognition while potentially sensitizing them to NK cells (though tumors often counter this via TME factors like TGF-β). This phenotype occurs in 40-90% of tumors, correlates with worse prognosis and reduced TILs, and contributes to resistance against immunotherapies like checkpoint inhibitors by creating immune deserts

Other names

MHC class I-deficient tumor cellsMHC-I low tumor cellsMHC-I-negative tumor cells