Cited by 899Cancer, Hypoxia, and MetabolismCancer Immunotherapy and BiomarkersImmune cells in cancer

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Metabolism of immune cells in cancer

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Leone, Robert D., Powell, Jonathan D.·2020·Nature Reviews Cancer

DOI 10.1038/s41568-020-0273-yPMC PMC8041116

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Abstract

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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Additional file 8 of Group-specific cellular metabolism in Medulloblastoma
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Additional file 6 of Group-specific cellular metabolism in Medulloblastoma
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Additional file 2 of Group-specific cellular metabolism in Medulloblastoma
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Additional file 7 of Group-specific cellular metabolism in Medulloblastoma
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Additional file 3 of Group-specific cellular metabolism in Medulloblastoma
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Additional file 5 of Group-specific cellular metabolism in Medulloblastoma
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Additional file 12 of Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma
Li, D., Yu, H., Hu, J., Li, S., Yan, Y., Li, S., Sun, L., Jiang, G., Hou, L., zhang, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21192112
Additional file 7 of Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma
Li, D., Yu, H., Hu, J., Li, S., Yan, Y., Li, S., Sun, L., Jiang, G., Hou, L., zhang, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21192139
Additional file 1 of Group-specific cellular metabolism in Medulloblastoma
Funke, V. L. E., Walter, C., Melcher, V., Wei, L., Sandmann, S., Hotfilder, M., Varghese, J., Jäger, N., Kool, M., Jones, D. T. W., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23298899
Additional file 8 of Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment
Song, Q., Yu, H., Cheng, Y., Han, J., Li, K., Zhuang, J., Lv, Q., Yang, X., & Yang, H. (2022) · Figshare · doi:10.6084/m9.figshare.20252780
Additional file 2 of Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment
Song, Q., Yu, H., Cheng, Y., Han, J., Li, K., Zhuang, J., Lv, Q., Yang, X., & Yang, H. (2022) · Figshare · doi:10.6084/m9.figshare.20252762
Additional file 11 of Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma
Li, D., Yu, H., Hu, J., Li, S., Yan, Y., Li, S., Sun, L., Jiang, G., Hou, L., Zhang, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21192109
Additional file 1 of Identification of two novel lipid metabolism-related long non-coding RNAs (SNHG17 and LINC00837) as potential signatures for osteosarcoma prognosis and precise treatment
Tang, Z., Feng, H., Shu, L., Guo, M., Qi, B., Pu, L., Shi, H., Ren, J., & Li, C. (2023) · Figshare · doi:10.6084/m9.figshare.23207814
Additional file 4 of Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature
He, J., Chen, Z., Xue, Q., Sun, P., Wang, Y., Zhu, C., & Shi, W. (2022) · Figshare · doi:10.6084/m9.figshare.19654696
Additional file 1 of Clinical significance and oncogenic function of NR1H4 in clear cell renal cell carcinoma
Huang, S., Hou, Y., Hu, M., Hu, J., & Liu, X. (2022) · Figshare · doi:10.6084/m9.figshare.21171509
Additional file 6 of Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature
He, J., Chen, Z., Xue, Q., Sun, P., Wang, Y., Zhu, C., & Shi, W. (2022) · Figshare · doi:10.6084/m9.figshare.19654702
Additional file 9 of Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma
Li, D., Yu, H., Hu, J., Li, S., Yan, Y., Li, S., Sun, L., Jiang, G., Hou, L., Zhang, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21192145
Additional file 1 of SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway
Shang, K., Ma, N., Che, J., Li, H., Hu, J., SUN, H., & Cao, B. (2024) · Figshare · doi:10.6084/m9.figshare.26581694
Additional file 3 of Clinical significance and oncogenic function of NR1H4 in clear cell renal cell carcinoma
Huang, S., Hou, Y., Hu, M., Hu, J., & Liu, X. (2022) · Figshare · doi:10.6084/m9.figshare.21171515
Additional file 10 of Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature
He, J., Chen, Z., Xue, Q., Sun, P., Wang, Y., Zhu, C., & Shi, W. (2022) · Figshare · doi:10.6084/m9.figshare.19654681
Additional file 3 of Identification of two novel lipid metabolism-related long non-coding RNAs (SNHG17 and LINC00837) as potential signatures for osteosarcoma prognosis and precise treatment
Tang, Z., Feng, H., Shu, L., Guo, M., Qi, B., Pu, L., Shi, H., Ren, J., & Li, C. (2023) · Figshare · doi:10.6084/m9.figshare.23207823
Additional file 8 of Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma
Li, D., Yu, H., Hu, J., Li, S., Yan, Y., Li, S., Sun, L., Jiang, G., Hou, L., zhang, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21192142
Additional file 9 of Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature
He, J., Chen, Z., Xue, Q., Sun, P., Wang, Y., Zhu, C., & Shi, W. (2022) · Figshare · doi:10.6084/m9.figshare.19654714
Additional file 3 of Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature
He, J., Chen, Z., Xue, Q., Sun, P., Wang, Y., Zhu, C., & Shi, W. (2022) · Figshare · doi:10.6084/m9.figshare.19654693
Additional file 10 of Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma
Li, D., Yu, H., Hu, J., Li, S., Yan, Y., Li, S., Sun, L., Jiang, G., Hou, L., zhang, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21192106
Additional file 3 of SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway
Shang, K., Ma, N., Che, J., Li, H., Hu, J., SUN, H., & Bangwei, C. (2024) · Figshare · doi:10.6084/m9.figshare.26581700
Additional file 13 of Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma
Li, D., Yu, H., Hu, J., Li, S., Yan, Y., Li, S., Sun, L., Jiang, G., Hou, L., zhang, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21192115
Additional file 2 of Identification of two novel lipid metabolism-related long non-coding RNAs (SNHG17 and LINC00837) as potential signatures for osteosarcoma prognosis and precise treatment
Tang, Z., Feng, H., Shu, L., Guo, M., Qi, B., Pu, L., Shi, H., Ren, J., & Li, C. (2023) · Figshare · doi:10.6084/m9.figshare.23207820
Additional file 1 of Identification of a novel lipid metabolism-related gene signature within the tumour immune microenvironment for breast cancer
Chang, X., & Xing, P. (2022) · Figshare · doi:10.6084/m9.figshare.19766412
Additional file 8 of Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature
He, J., Chen, Z., Xue, Q., Sun, P., Wang, Y., Zhu, C., & Shi, W. (2022) · Figshare · doi:10.6084/m9.figshare.19654708

Authors: Leone, R. D., & Powell, J. D.
Affiliations: Johns Hopkins University (US)
Corresponding author: Powell, Jonathan D.
ORCID: Leone, Robert D.
Powell, Jonathan D.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2020-07-06
Volume: 20
Issue: 9
Pages: 516-531
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/s41568-020-0273-y
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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