CBDV modulates myeloid suppressor cells in the tumor microenvironment
During solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Therefore, the modulation of immunosuppressive cells in the TME to create a more active environment is a compelling strategy for preventing tumor progression. Here, we found that Cannabidivarin (CBDV), a minor cannabinoid, directly reduces the immunosuppressive properties of MDSCs and shifted their differentiation from TAMs to M1-like macrophages. Treating myeloid suppressor cells with CBDV led to restored CD8+ T-cell activation and proliferation in a co-culture model. Tumor-bearing mice treated with CBDV presented reduced tumor progression, and myeloid suppressor cells in the TME showed a reduction in immunosuppressive markers, in line with enhancing CD8+ T-cell activity. CBDV was also effective in human cells, reducing immunosuppressive markers by human myeloid suppressor cells. Altogether, our findings indicate CBDV holds the potential to reprogram immune system cells within the TME to strengthen the immune response against cancer.