Administration of cannabinoids enhances growth and metastasis of 4T1 murine breast cancer through the induction of myeloid derived suppressor cells. (100.2)

Breast cancer is the most prevalent type of cancer afflicting women with more than 190,000 new cases diagnosed per year and over 40,000 deaths. The active ingredient in marijuana (Cannabis sativa), delta9-tetrahydrocannabinol (THC) as well as endogenous cannabinoids, such as anandamide, have been shown to exert effects on immune cells that express the cannabinoid(CB) receptors. We have previously shown that when mice are inoculated with 4t1 murine mammary carcinoma and treated with THC, the tumor grows and metastasizes more rapidly when compared to vehicle controls, resulting from immunosuppression. However, the mechanism for the loss of immune surveillance following THC treatment is not clear. Upon treatment of tumor-bearing mice, there was a significant increase in primary tumor size following THC treatment when compared to controls. Histopathological analysis demonstrated more tumor nodules in the lungs in groups exposed to THC. The splenocytes and pulmonary lymphocytes were assessed for the presence of MDSCs. There was an increase in MDSC in the lungs and spleens in cannabinoid-treated mice when compared to controls. Our studies therefore demonstrated that 4T1 mammary tumor-bearing mice elicited the development of MDSC in the spleens and lungs and the frequency of these cells was enhanced following administration of THC. Thus, we suggest a role for MDSCs in the cannabinoid-induced immune suppression in breast cancer patients that may result in enhanced tumor growth.