A single Cannabinoid reduces Melanoma secretion of CSF-1 leading to decreased MDSC immunosuppressive Activity

Key players in establishing the immunosuppressive tumor microenvironment are Myeloid-derived suppressor cells (MDSC). One promising strategy targeting MDSC is the depletion of tumor secreted cytokines to achieve a reduction in their recruitment and activation. A few studies examined the ability of single cannabinoids to affect MDSC in healthy mice or immune-related diseases. However, the effect of whole cannabis extracts or single cannabinoids on the MDSC population in a tumor model was not assessed.

In this study we aim to investigate how Medical Cannabis (MC) extracts influence MDSC population´s frequency and activity by using the highly immunogenic murine melanoma cell line B16F10 model and the ex-vivo generation of MDSC from bone-marrow derived cells.

Our preliminary results show the reduced secretion of several myeloid-related cytokines by B16F10 when treated with a whole MC extract. Further in-vivo and in-vitro validation showed the specific reduction of Colony Stimulating Factor-1 (CSF-1) after treatment. We then used the fractionation method developed in our lab and managed to identify a specific cannabinoid (315-1a) responsible for reducing CSF-1 secretion. Further, we tested if the reduced CSF-1 secretion by B16F10 treated with 315-1a affect MDSC activity ex-vivo.

The specific reduction of CSF-1 secretion by melanoma cells treated with 315-1a resulted in reduced iNOS expression by the subpopulation of Monocytic-MDSC, leading to restored T-cell proliferation.

We are currently exploring CD8+ frequencies and activation in tumors of 315-1a treated mice. Moreover, we are exploring the synergistic effect of 315-1a together with commonly used immunotherapeutic agents, such as anti-PD1, on tumor progression.