Cannabidiol (CBD) as a novel inhibitor of HLA-G expression in human choriocarcinoma cell line (JEG-3)

Cannabinoids have emerged as promising agents in cancer research due to their antitumor properties. While their effects on tumor growth and survival have been widely investigated, their impact on immune checkpoint regulation remains largely unexplored. In this study, we examined the effects of cannabidiol (CBD) and a high-CBD extract (CBD-HCE) on the expression of HLA-G in human choriocarcinoma JEG-3 cells. HLA-G is a non-classical HLA class I molecule associated with immune escape in tumors. Both CBD and CBD-HCE were found to reduce cell proliferation and migration, increase apoptosis, and significantly downregulate HLA-G expression at both the mRNA and protein levels. This inhibitory effect was observed to be both dose- and time-dependent, and it was completely reversible after the treatment was removed, indicating a dynamic and CBD-dependent modulation. These results provide the first experimental evidence of HLA-G downregulation by CBD and CBD-HCE, highlighting a novel immunomodulatory mechanism with potential therapeutic implications. By simultaneously targeting tumor cell viability and immune evasion, CBD-based compounds may enhance antitumor immune responses and improve the efficacy of immunotherapies. Further research involving additional tumor cell lines, in vivo models, and immune-relevant systems are necessary to validate and expand upon these findings.