杀伤细胞免疫球蛋白样受体（KIR）基因和人类白细胞抗原（HLA）I 类配体对前列腺癌易感性或保护作用的影响

Natural killer (NK) cell development largely depends on killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. In the current study, we investigated the role of KIR genes, HLA ligands, and KIR-HLA combinations in vulnerability or protection against prostate cancer (PC). To analyze the frequency of 16 KIR genes and 5 HLA ligands, polymerase chain reaction with sequence-specific primers (PCR-SSP) was conducted in 150 PC patients and 200 healthy controls (CNs).

KIR2DL5 (p = 0. 0346, OR = 0. 606, CI = 0. 3916-0. 9336), KIR2DS5 (p = 0. 0227, OR = 0. 587, CI = 0. 3793-0. 9139), HLA-B Bw4 Thr80 (p = 0. 0401, OR = 0. 3552, CI = 0. 1466-0. 9059), HLA Bw4 (p = 0. 0190, OR = 0. 4744, CI = 0. 2656-0. 8521), and T4 gene cluster (including KIR2DS5-2DL5-3DS1-2DS1 genes) (p = 0. 0194, OR = 0. 5575, CI = 0. 3449-0. 8938) had a lower frequency in the PC patients compared to the control group.

Moreover, a lower frequency of the genotypes contacting activating KIR (aKIR) > inhibitory KIR (iKIR) (p = 0. 0298, OR = 0. 5291, CI = 0. 3056-0. 9174) and iKIR + HLA < aKIR + HLA (p = 0. 0183, OR = 0. 2197, CI = 0. 0672-0. 7001) in PC patients compared to the CNs implies a protective role for aKIR genes. In the case of KIR-HLA interactions, we detected a significant association between KIR3DS1 + + HLA-A Bw4 + (p = 0. 0113, OR = 0. 5093, CI = 0. 3124-0. 8416) and KIR3DL1 - + HLA-A Bw4 + (p = 0. 0306, OR = 0. 1153, CI = 0. 0106-0. 6537) combinations and resistance to prostate cancer. In contrast, the presence of KIR3DL1 in the absence of HLA-A Bw4 (p = 0.

0040, OR = 2. 00, CI = 1. 264-3. 111), HLA Bw4 (p = 0. 0296, OR = 2. 066, CI = 1. 094-3. 906), and HLA-Bw4 Thr80 (p = 0. 0071, OR = 2. 505, CI = 1. 319-4. 703) genes probably predisposes to prostate cancer. Carrying the CxT4 genotype in PC patients was positively associated with lower tumor grades (Gleason score ≤ 6) (p = 0.

0331, OR = 3. 290, and CI = 1. 181-8. 395). Altogether, our data suggest a protective role for aKIRs, HLA-B Bw4 Thr80 , and HLA Bw4 ligands as well as a predisposing role for certain KIR-HLA combinations in prostate cancer. The findings of this study offer new insight into the population's risk assessment for prostate cancer in men.

Additionally, predicting immunotherapy response based on KIR-HLA combinations aids in implementing the most effective therapeutic approach in the early stages of the disease.