Can human leukocyte antigen G be widely accepted as a biomarker in cancer clinical practice?

Human Leukocyte Antigen G (HLA-G) is a non-classical HLA class I molecule that was first explored in reproductive immune regulation for fetal implantations [1]. Because HLA-G has immune suppressive functions, it has been assumed that HLA-G could play a role in tumor immune escape mechanisms. Thirty years ago, Paul et al. [2] first reported that HLA-G expression was specifically observed in melanoma lesions. Since then, numerous subsequent studies with thousands of samples from more than thirty different types of tumors have demonstrated that HLA-G expression in cancers is highly related to immune suppressive microenvironments, advanced tumor stages, and poor therapeutic responses and prognosis [3]. Accordingly, HLA-G has been recommended to be a novel biomarker for the diagnosis, prognosis, and tumor immune escape of human cancers.