Pparγ inhibition boosts efficacy of pd-l1 checkpoint blockade immunotherapy against murine melanoma in a sexually dimorphic manner

Bogang Wu, Xiujie Sun, Bin Yuan, Fei Ge, Harshita B. Gupta, Huai Chin Chiang, Jingwei Li, Yanfen Hu, Tyler J. Curiel, Rong Li

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1526-1535
Number of pages10
JournalInternational Journal of Biological Sciences
Volume16
Issue number9
DOIs
StatePublished - 2020

Keywords

  • Immunotherapy
  • Melanoma
  • Obesity
  • PD-L1
  • PPARγ
  • Sexual dimorphism

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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