Chorionic Gonadotropin Beta 7 is a marker of immune evasion in cancer

Human chorionic gonadotropin beta (beta-hCG) is an oncofetal antigen expressed by trophoblast cells of the placenta, with minimal expression in adult somatic tissues. Numerous studies have demonstrated that beta-hCG-encoding genes are expressed in various cancers, but expression of these genes (CGB3,CGB5,CGB7, andCGB8) across diverse cancers has not been systematically evaluated. Here, we report that CGB genes are more widely expressed across diverse cancer types than previously appreciated and that secreted beta-hCG is readily detected. In particular, CGB genes are expressed in the majority of urothelial bladder cancers, whereCGB7is most frequently expressed and significantly associated with an immunosuppressed tumor microenvironment, including decreased CD8⁺T cell infiltration. Multiple CGB genes are associated with failure to respond to immune checkpoint inhibitor (ICI) therapy, andCGB7is particularly strongly predictive of poor prognosis. Overall, our findings indicate that beta-hCG is a clinically accessible, predictive biomarker of immunotherapeutic response.