Journal
NATURE IMMUNOLOGY
Volume 21, Issue 3, Pages 298-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41590-019-0589-5
Keywords
-
Categories
Funding
- SNSF [31003A_163204, 31003A_182470, PMPDP3_129022, PZ00P3_161459, 320030_162575]
- Swiss Cancer Foundation [KFS-3949-08-2016]
- Swiss Institute for Experimental Cancer Research [ISREC 26075483]
- European Research Council [802773-MitoGuide]
- Cancer Research Institute Clinic and Laboratory Integration Program award
- SITC-MRA Young Investigator Award
- Cancer League Switzerland [KFS-3394-02-2014]
- NIH [P01 HL46403, P01 HL087018, R01 HL142152, HL45095, HL073029, P30 CA008748, R01 CA056821]
- Swiss Cancer Research Foundation [KFS-3681-08-2015-R]
- FWO
- KU Leuven Methusalem
- Swim Across America
- Ludwig Institute for Cancer Research
- Parker Institute for Cancer Immunotherapy
- Breast Cancer Research Foundation
- Parker Institute for Cancer Immunotherapy Bridge Scholar Award
- Electron Microscopy Facility at the University of Lausanne
- Biomedical Sequencing Facility at the Research Center for Molecular Medicine of the Austrian Academy of Sciences
- Swiss National Science Foundation (SNF) [PMPDP3_129022, PZ00P3_161459, 320030_162575] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
Depleting regulatory T cells (T-reg 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 T-reg cells is direly needed for cancer immunotherapy. We found that CD36 was selectively upregulated in intrautumoral T-reg cells as a central metabolic modulator. CD36 fine-tuned mitochondrial fitness via peroxisome proliferator-activated receptor-beta signaling, programming T-reg cells to adapt to a lactic acid-enriched TME. Genetic ablation of Cd36 in T-reg cells suppressed tumor growth accompanied by a decrease in intratumoral T-reg 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 T-reg cells, and the therapeutic potential of targeting this pathway for reprogramming the TME. Tumor environments are highly acidic due to high concentrations of lactic acid. Ho and colleagues report that tumor-infiltrating regulatory T cells adapt to this tumor environment by upregulating expression of CD36, which allows them to use fatty acids to fuel their metabolism.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available