Assessment of killer-cell immunoglobulin-like receptor (KIR) polymorphisms and their HLA-ligands in epithelial ovarian cancer (EOC).

Abstract

e17580 Background: EOC carcinogenesis involves the progressive accumulation of genetic, epigenetic, and molecular alterations, resulting in heterogeneous expression of tumor-associated antigens, suggesting a role of the immune system in tumor development and progression. Natural Killer–cell mediated tumor surveillance depends on the balance between inhibitory and activating signals. In this context, characterization of KIR polymorphisms and their HLA ligands may be crucial to understand their influence on EOC susceptibility and prognosis. This study aimed to evaluate the role of KIR polymorphisms and HLA ligands in EOC. Methods: This retrospective longitudinal study included 118 women: 64 EOC patients treated at Hospital Reina Sofia, from 2020 to 2023, and 54 controls. Differences in the distribution of KIR polymorphisms and HLA-A, -B, and -C ligands were analyzed according to disease presence. In the patient group, the association of these variables with a previously established prognostic factor was evaluated: platinum-free interval until relapse (PFI). Clinical and pathological data were analyzed using Kaplan-Meier, Long-rank and Chi-square/Fisher test. Results: HLA-A*11:01 was significantly associated with EOC diagnosis (OR 3.13; 95% CI 1.14–8.58; p=0.022), whereas HLA-B*38:01 was associated with absence of disease (OR 0.19; 95% CI 0.04–0.92; p=0.042). Regarding PFI, HLA-A*23:01, HLA-A*29:02, and HLA-B*37:01 were associated with shorter PFI, while HLA-B*44:03 was associated with longer PFI; as shown in table. With a median follow-up of 50 months (m), univariate survival analysis showed significantly poorer overall survival in carriers of HLA-B*37:01 (4 vs 102 m; p<0.001). A non-significant trend toward shorter survival was observed among HLA-A*29:02 carriers (48 vs 102 m; p=0.191). No significant associations were observed for KIR. Conclusions: Specific HLA ligands may influence both susceptibility and prognosis in EOC. HLA-A*11:01 appears to increase disease risk, while HLA-B*38:01 may exert a protective effect. Moreover, HLA-A*23:01, HLA-A*29:02, and HLA-B*37:01 are associated with shorter PFI, with HLA-B*37:01 also correlating with poorer survival. These findings suggest a potential role of HLA in EOC and may justify further investigation into its relevance for prognostic stratification and personalized therapies. PFI < 6 m PFI > 6 m N N p OR (CI 95%) HLA-A*23:01 Positive: 2Negative: 11 Positive: 0Negative: 51 0,039 0,177 (0,104-0,303) HLA-A*29:02 Positive: 5Negative: 8 Positive: 4Negative: 47 0,013 0,136 (0,030-0,619) HLA-B*37:01 Positive: 3Negative: 10 Positive: 0Negative; 51 0,007 0,164 (0,093-0,289) HLA-B*44:03 Positive: 5Negative: 8 Positive: 7Negative: 44 0,041 0,255 (0,065-1,005)