Tumor cells with reduced MHC class I expression or increased stress ligands (MHC-low/Stress-high tumor cells)

This target refers to a specific cellular phenotype rather than a single molecule, characterized by the downregulation of Major Histocompatibility Complex (MHC) class I molecules and the concomitant upregulation of stress-induced ligands such as MICA, MICB, and ULBPs (PMID: 18552865). MHC class I molecules are essential for presenting intracellular antigens to CD8+ T cells; their reduction is a hallmark of cancer immune evasion, allowing tumors to bypass adaptive immune surveillance (PMID: 30104726). However, this loss of 'self' markers, combined with the expression of stress ligands, renders these cells primary targets for Natural Killer (NK) cells through the activation of receptors like NKG2D (PMID: 21148347). Therapeutic strategies targeting this phenotype include adoptive transfer of NK cells, CAR-NK cell therapies, and the use of epigenetic modifiers like HDAC inhibitors to further upregulate stress ligands and enhance immune recognition (PMID: 23708335).

Other names

MHC-I deficient tumor cellsMHC-I downregulated cancer cellsStress-ligand expressing tumor cellsNK cell-sensitive tumor cellsMissing-self phenotype cells

Therapeutic interventions exploit the 'missing self' (lack of MHC I inhibitory signaling) and 'induced self' (presence of stress ligands) signals to trigger NK cell-mediated or CAR-mediated cytotoxicity against the tumor cells.