Influence of immune-checkpoint inhibitor and HLA-G in patients with Cervical Cancer

Abstract

Abstract A better understanding of the role of Immune checkpoint inhibitors (ICI) and immunoregulatory genes HLA-G is essential for the development of immunotherapeutic strategies in cancer. This study aims to evaluate the influence of CTLA-4, PD-1 and polymorphisms of HLA-G and soluble HLA-G (sHLA-G) in patients with cervical cancer (CC), different degrees of Cervical Intraepithelial Neoplasia (CIN), and healthy control (HC). One hundred and seventy-four (174) non-pregnant Brazilian women, sexually active, older than 18 years, were evaluated. These patients were stratified according to the results of the anatomopathological examination in: CC group n=24, Low-grade squamous intraepithelial lesions (LSIL) n=66, High-grade squamous intraepithelial lesions (HSIL) n=84. HC group consisted of 47 women without cytological and/or colposcopic abnormalities detected. The peripheral blood of these patients was collected for analysis of CTLA-4, PD-1 and HLA-G polymorphisms using real-time PCR. The analysis indicated a significantly higher 14bpDel allele frequency in CC when compared to HC group (P=0.030, OR=1.71, 95%CI 1.01–2.74). Moreover, the 14bpDel/Del genotype frequency was also significantly higher in patients with CC group (P = 0.035, OR=2.23, 95%CI 1.05–4.97). Qualitative analysis revealed that the production of sHLA-G is detectable in 52.03% (n=77) of all patients groups and 34.29 %(n=12) in HC groups. This analysis revealed a trend of significance (P= 0.063; OR=2.08, 95%CI=0.96–4.48) in CC group. The polymorphisms of CTLA-4 and 14 bp HLA-G are associated with a significantly increased risk of CC. HLA-G 14bp Del/Del polymorphism, and the serum sHLA-G can act as a promising biomarker for might be a genetic risk factor for CC.