HLA superfamily assignment is a predictor of immune response to cancer testis antigens and survival in ovarian cancer

• HLA-B27 superfamily assignment is associated with ovarian cancer risk
• Assignment to HLA-B44 superfamily is associated with worse prognosis
• Certain HLA superfamily assignments may be more sensitive to immunotherapy

ObjectivesTo characterize the association between major histocompatibility complex (MHC) types and spontaneous antibody development to the cancer testis (CT) antigen NY-ESO-1.MethodsTumor expression of NY-ESO-1 and serum antibodies to NY-ESO-1 were characterized in addition to human leukocyte antigen (HLA) type for patients with epithelial ovarian cancer. HLA types were assigned to structure-based superfamilies and statistical associations were examined. HLA types were compared to existing reference libraries of HLA frequencies in a European-Caucasian American population.ResultsOut of 126 patients identified, 81% were expression positive and 48% had spontaneous antibody responses to NY-ESO-1. There was an association between HLA-B superfamily and seropositivity among patients with tumors expressing NY-ESO-1 (p < 0.001). The differences in HLA-B superfamily assignment were driven by HLA-B44. Among all patients, the B27 superfamily was over-represented compared with the general population (p < 0.001).ConclusionsHLA type appears to be associated with spontaneous anti-CT antigen antibodies, as well as with the overall risk of ovarian cancer.