The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors
Open accessAbstract
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. 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.
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Self-citationPhosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses
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Self-citationA Special Population of Regulatory T Cells Potentiates Muscle Repair
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Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy
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Turning cold tumors hot: from molecular mechanisms to clinical applications
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Metabolic and epigenetic regulation of T-cell exhaustion
Franco, F., Jaccard, A., Romero, P., Yu, Y.-R., & Ho, P.-C. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00280-9 · Cited by 455
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Metadata
- Authors
- Wang, H., Franco, F., Tsui, Y.-C., Xie, X., Trefny, M. P., Zappasodi, R., Mohmood, S. R., Fernández-García, J., Tsai, C.-H., Schulze, I., Picard, F., Meylan, E., Silverstein, R., Goldberg, I., Fendt, S.-M., Wolchok, J. D., Merghoub, T., Jandus, C., Zippelius, A., & Ho, P.-C.
- Venue
- Nature Immunology
- Published
- 2020-02-17
- Volume
- 21
- Issue
- 3
- Pages
- 298-308
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W3006222581
- Cited by
- 672
- References
- 16
- FWCI
- 22.76
- Type
- journal article
- Language
- en
- Open access
- green
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- Wang, H., Franco, F., Tsui, Y.-C., Xie, X., Trefny, M. P., Zappasodi, R., Mohmood, S. R., Fernández-García, J., Tsai, C.-H., Schulze, I., Picard, F., Meylan, E., Silverstein, R., Goldberg, I., Fendt, S.-M., Wolchok, J. D., Merghoub, T., Jandus, C., Zippelius, A., & Ho, P.-C. (2020). CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors. Nature Immunology. https://doi.org/10.1038/s41590-019-0589-5
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