HLA-E
Overview
HLA-E encodes a non-classical MHC class I molecule that engages the inhibitory NKG2A receptor on NK cells and CD8+ T cells, suppressing cytotoxicity. In HGSOC, HLA-E is progressively upregulated from the earliest precursor stages and is proposed as a key immune evasion mechanism.
Alterations observed in the corpus
- HLA-E is progressively upregulated across HGSOC progression: p53 signature (median 4% HLA-E+ epithelial cells) to STIC.C (26%); upregulation is strongly associated with IFN and IRDS gene signatures PMID:39386723.
- HLA-E-positive tumor regions are characterized by decreased NK cell infiltration (nearly undetectable NK cells in STIC.I, STIC.C, and cancer; median 0.02% vs 0.1% in normal/p53.I), consistent with NKG2A-mediated immune suppression PMID:39386723.
Cancer types (linked)
- HGSOC — progressive upregulation from p53 signatures through invasive cancer; proposed mechanism for NK cell evasion; potential early interception target with anti-NKG2A antibodies (e.g., monalizumab) in high-risk incidental STIC patients PMID:39386723.
Co-occurrence and mutual exclusivity
- Co-upregulated with classical MHC-I (HLA-A), IFITM1, IRF7, IRF9, ISG15, STAT1 as part of IFN pathway activation PMID:39386723.
- HLA-E upregulation is independent of EMT and TGF-beta pathway emergence (which occurs primarily at STIC.C/cancer stages) PMID:39386723.
Therapeutic relevance
- Anti-NKG2A antibodies (e.g., monalizumab) represent a candidate early-interception strategy targeting the HLA-E/NKG2A immune evasion axis in HGSOC precursors, particularly for high-risk patients with incidental STICs PMID:39386723.
Open questions
- Functional validation of the proposed HLA-E/NKG2A immune evasion axis in HGSOC precursors is needed PMID:39386723.
- The relative contribution of HLA-E vs other immune suppressive mechanisms (Treg accumulation, CD8+ T cell exhaustion) to the overall immune evasion in HGSOC is unresolved PMID:39386723.
Sources
This page was processed by crosslinker on 2026-05-04.