标题：Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk
摘要：Human leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell function in eliminating malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in peripheral blood. To test the hypothesis that certain
KIR-HLA combinations impairing NK-cytotoxicity predispose to BC risk, we analyzed
KIR and
HLA polymorphisms in 162 women with BC and 278 controls.
KIR-Bx genotypes increased significantly in BC than controls (83.3% vs. 71.9%, OR 1.95), and the increase was more pronounced in advanced-cancer (OR 5.3). No difference was observed with inhibitory
KIR (
iKIR) and
HLA-ligand combinations. The activating
KIR (
aKIR) and HLA-ligand combinations,
2DS1 +
C2 (OR 2.98) and
3DS1 +
Bw4 (OR 2.6), were significantly increased in advanced-BC. All patients with advanced-cancer carrying
2DS1 +
C2 or
3DS1 +
Bw4 also have their
iKIR counterparts
2DL1 and
3DL1, respectively. Contrarily, the
2DL1 +
C2 and
3DL1 +
Bw4 pairs without their
aKIR counterparts are significantly higher in controls. These data suggest that NK cells expressing iKIR to the cognate HLA-ligands in the absence of putative aKIR counterpart are instrumental in antitumor response. These data provide a new framework for improving the utility of genetic risk scores for individualized surveillance.
