CBD Shrunk HPV-Positive Head and Neck Tumors by Boosting Immune Response in Mice

CBD activated the MAPK pathway (ERK1/2, JNK/SAPK, MK2), promoting apoptosis in cancer cells. In immunocompetent mice, CBD significantly reduced tumor growth and enhanced infiltration of CD4+T cells, CD8+T cells, B cells, NK cells, and M1-like macrophages. No anti-tumor effect was seen in immune-deficient mice. CD4+ T cell depletion reversed CBD's benefit, confirming immune dependence.

In vitro: BrdU proliferation, apoptosis, migration, and western blot analyses on HPV-positive HNSCC cells. In vivo: syngeneic mouse models (immunocompetent), Rag1 knockout mice (no T/B cells), and athymic nude mice (no T cells). Immune depletion experiments targeted CD4+ and CD8+ T cells. Flow cytometry, IHC, and multiplex IHC measured immune infiltration.

This is the first preclinical demonstration that CBD's anti-tumor activity in HPV-positive head and neck cancer depends entirely on the immune system rather than direct cancer cell killing alone. This has implications for combining CBD with immunotherapy approaches.

HPV-positive head and neck cancers are increasing globally. The finding that CBD's anti-cancer effect is immune-mediated opens the possibility of combining CBD with checkpoint inhibitors or other immunotherapies, potentially enhancing treatment responses in this growing patient population.

Mouse models do not fully recapitulate human HPV-positive HNSCC. CBD doses and routes used in mice may not translate to achievable human concentrations. Syngeneic models use mouse cancer cells, not human tumors. No comparison with standard of care treatments. Association between marijuana use and HPV-positive HNSCC adds complexity to clinical translation.