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Metabolism of immune cells in cancer
Open accessAbstract
Through the successes of checkpoint blockade and adoptive cellular therapy, immunotherapy has become an established treatment modality for cancer. Cellular metabolism has emerged as a critical determinant of the viability and function of both cancer cells and immune cells. In order to sustain prodigious anabolic needs, tumours employ a specialized metabolism that differs from untransformed somatic cells. This metabolism leads to a tumour microenvironment that is commonly acidic, hypoxic and/or depleted of critical nutrients required by immune cells. In this context, tumour metabolism itself is a checkpoint that can limit immune-mediated tumour destruction. Because our understanding of immune cell metabolism and cancer metabolism has grown significantly in the past decade, we are on the cusp of being able to unravel the interaction of cancer cell metabolism and immune metabolism in therapeutically meaningful ways. Although there are metabolic processes that are seemingly fundamental to both cancer and responding immune cells, metabolic heterogeneity and plasticity may serve to distinguish the two. As such, understanding the differential metabolic requirements of the diverse cells that comprise an immune response to cancer offers an opportunity to selectively regulate immune cell function. Such a nuanced evaluation of cancer and immune metabolism can uncover metabolic vulnerabilities and therapeutic windows upon which to intervene for enhanced immunotherapy. This Review discusses our current understanding of adaptive and innate immune cell metabolism in the context of the tumour microenvironment, providing insight into the interaction of cancer cell metabolism and immune metabolism, as well as the potential for leveraging metabolic vulnerabilities to enhance the antitumour immune response.
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“Similarly, HIF-2α directly upregulates PD-L1 expression by binding to the HRE in the PD-L1 promoter in ccRCC cells (Fig. 2C) [73].”
From Revisiting the HIF switch in the tumor and its immune microenvironment. (2022) · cites this paper as [73]
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Metadata
- Authors
- Leone, R. D., & Powell, J. D.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Powell, Jonathan D.
- Venue
- Nature Reviews Cancer
- Published
- 2020-07-06
- Volume
- 20
- Issue
- 9
- Pages
- 516-531
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC8041116
- OpenAlex
- W3040651070
- Semantic Scholar
- 9e54633c23933564226222b58eee14bffccca97c
- Cited by
- 877
- References
- 228
- Citations by year
- 2026: 137 · 2025: 168 · 2024: 141 · 2023: 135 · 2022: 185 · 2021: 98 · 2020: 12
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA229451, R01CA226765)
- National Institute of Allergy and Infectious Diseases (R01AI077610)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- immune cell metabolism, cancer metabolism, tumor microenvironment, tumor acidosis, tumor hypoxia, nutrient depletion, adaptive immunity, innate immunity, metabolic heterogeneity, metabolic plasticity, metabolic vulnerability, immunotherapy, antitumor immunity
- MeSH terms
- Animals, Humans, Immune System, Immunotherapy, Neoplasms, Tumor Microenvironment
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