MHC class I–deficient tumor cells (MHC-I deficient tumor cells)

MHC class I–deficient tumor cells represent a specific cancer phenotype characterized by the partial or total loss of Major Histocompatibility Complex (MHC) class I molecule expression on the cell surface (Garrido et al., 2016). This downregulation is a hallmark of cancer immune evasion, as MHC-I molecules are essential for presenting intracellular tumor antigens to CD8+ cytotoxic T lymphocytes (CTLs); without them, the adaptive immune system cannot effectively identify or eliminate the malignancy (Cornel et al., 2020). While this loss provides a survival advantage against T-cell-mediated attacks, it simultaneously makes these cells primary targets for Natural Killer (NK) cells through the 'missing self' recognition mechanism (Ljunggren and Kärre, 1990). Therapeutic approaches specifically targeting these cells include the use of adoptive NK cell transfers, CAR-NK therapies, and agents like Interferon-gamma that may upregulate MHC expression. Identifying MHC-I deficiency is a critical biomarker in clinical oncology, as it often correlates with resistance to conventional immune checkpoint inhibitors such as PD-1/PD-L1 blockers (Garrido et al., 2016).

Other names

HLA class I-deficient tumor cellsMHC-I negative cancer cellsMHC-I low tumor cellsBeta-2 microglobulin (B2M) deficient tumor cellsMHC-I deficient cancer cells

Natural Killer (NK) cell-mediated cytotoxicity via the 'missing self' hypothesis, where the absence of MHC-I-mediated inhibitory signaling through Killer-cell Immunoglobulin-like Receptors (KIRs) leads to NK cell activation and tumor lysis (Ljunggren and Kärre, 1990).