CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors

Haiping Wang, Fabien Franco, Yao Chen Tsui, Xin Xie, Marcel P. Trefny, Roberta Zappasodi, Syed Raza Mohmood, Juan Fernández-García, Chin Hsien Tsai, Isabell Schulze, Florence Picard, Etienne Meylan, Roy Silverstein, Ira Goldberg, Sarah Maria Fendt, Jedd D. Wolchok, Taha Merghoub, Camilla Jandus, Alfred Zippelius, Ping Chih Ho

Research output: Contribution to journalArticlepeer-review


Depleting regulatory T cells (Treg cells) to counteract immunosuppressive features of the tumor microenvironment (TME) is an attractive strategy for cancer treatment; however, autoimmunity due to systemic impairment of their suppressive function limits its therapeutic potential. Elucidating approaches that specifically disrupt intratumoral Treg cells is direly needed for cancer immunotherapy. We found that CD36 was selectively upregulated in intrautumoral Treg cells as a central metabolic modulator. CD36 fine-tuned mitochondrial fitness via peroxisome proliferator-activated receptor-β signaling, programming Treg cells to adapt to a lactic acid-enriched TME. Genetic ablation of Cd36 in Treg cells suppressed tumor growth accompanied by a decrease in intratumoral Treg cells and enhancement of antitumor activity in tumor-infiltrating lymphocytes without disrupting immune homeostasis. Furthermore, CD36 targeting elicited additive antitumor responses with anti-programmed cell death protein 1 therapy. Our findings uncover the unexplored metabolic adaptation that orchestrates the survival and functions of intratumoral Treg cells, and the therapeutic potential of targeting this pathway for reprogramming the TME.

Original languageEnglish (US)
Pages (from-to)298-308
Number of pages11
JournalNature Immunology
Issue number3
StatePublished - Mar 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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