Pparγ inhibition boosts efficacy of pd-l1 checkpoint blockade immunotherapy against murine melanoma in a sexually dimorphic manner
International Journal of Biological Sciences
Immunotherapy; Melanoma; Obesity; PD-L1; PPARγ; Sexual dimorphism
Immune checkpoint blockade-based immunotherapy has become standard of care for multiple cancer types. However, the overall response rates among various cancer types still remain unsatisfactory. There is a pressing clinical need to identify combination therapies to improve efficacy of anticancer immunotherapy. We previously showed that pharmacologic inhibition of PPARγ by GW9662 boosts αPD-L1 and αPD-1 antibody efficacy in treating murine mammary tumors. In addition, we defined sexually dimorphic αPD-L1 efficacy in B16 melanoma. Here, we show a sexually dimorphic response to the combination of GW9662 and αPD-L1 immunotherapy in B16 melanoma. Combination effects were observed in female, but not male hosts. Neither female oöphorectomy impairs, nor does male castration rescue the combination effects, suggesting a sex hormone-independent response to this combination therapy. In diet-induced obese females, melanoma growth remained responsive to the combination treatment, albeit less robustly than lean females. These findings are informative for future design and application of immunotherapy-related combination therapy for treating human melanoma patients by taking gender and obesity status into consideration.
Wu, B., Sun, X., Yuan, B., Ge, F., Gupta, H., Chiang, H., Li, J., Hu, Y., Curiel, T., & Li, R. (2020). Pparγ inhibition boosts efficacy of pd-l1 checkpoint blockade immunotherapy against murine melanoma in a sexually dimorphic manner. International Journal of Biological Sciences, 16 (9). http://dx.doi.org/10.7150/ijbs.42966