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PPARγ inhibition boosts efficacy of PD-L1 Checkpoint Blockade Immunotherapy against Murine Melanoma in a sexually dimorphic manner.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2020 Mar 05; Vol. 16 (9), pp. 1526-1535. Date of Electronic Publication: 2020 Mar 05 (Print Publication: 2020). - Publication Year :
- 2020
-
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.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Anilides therapeutic use
Animals
Diet, High-Fat adverse effects
Female
Immunotherapy
Male
Melanoma, Experimental complications
Mice, Inbred C57BL
Obesity complications
Obesity etiology
Antineoplastic Combined Chemotherapy Protocols therapeutic use
B7-H1 Antigen antagonists & inhibitors
Immune Checkpoint Inhibitors therapeutic use
Melanoma, Experimental therapy
PPAR gamma antagonists & inhibitors
Sex Characteristics
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 16
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32226299
- Full Text :
- https://doi.org/10.7150/ijbs.42966