KLRK1
Overview
KLRK1 encodes NKG2D, an activating C-type lectin receptor expressed on NK cells, CD8+ T cells, and NKT cells. NKG2D-mediated cytotoxicity is a key mechanism of immune surveillance against stressed or transformed cells. In HGSOC, declining NKG2D (KLRK1) expression marks progressive NK cell dysfunction.
Alterations observed in the corpus
- KLRK1 (NKG2D) expression declined in STIC.C and invasive cancer stages in HGSOC fallopian tube specimens, indicating progressive NK cell dysfunction; NK cells became nearly undetectable in STIC.I, STIC.C, and cancer (median 0.02% of cells vs 0.1% in normal/p53.I) PMID:39386723.
Cancer types (linked)
- HGSOC — KLRK1 expression loss marks progressive NK cell dysfunction from STIC stages through invasive cancer; studied in 44 FFPE fallopian tube specimens from 43 individuals using CyCIF (31-antibody panel) PMID:39386723.
Co-occurrence and mutual exclusivity
- KLRK1 decline co-occurs with progressive HLA-E upregulation in HGSOC precursors, consistent with NKG2A-mediated inhibition of NK cell cytotoxicity overriding NKG2D activation PMID:39386723.
Therapeutic relevance
- NK cell reactivation strategies that restore NKG2D-mediated surveillance (e.g., anti-NKG2A antibodies such as monalizumab) could counteract the progressive NK cell dysfunction evidenced by declining KLRK1 expression in HGSOC PMID:39386723.
Open questions
- Whether the decline in KLRK1 expression reflects loss of NK cells, NK cell exhaustion, or transcriptional downregulation within surviving NK cells in HGSOC precursors is unresolved PMID:39386723.
Sources
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