Cited by 576T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersMitochondrial Function and Pathology

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Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen

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Vardhana, Santosha A., Hwee, Madeline A., Berisa, Mirela, Wells, Daniel K., Yost, Kathryn E., King, Bryan, Smith, Melody, Herrera, Pamela S., Chang, Howard Y., Satpathy, Ansuman T., van den Brink, Marcel R. M., Cross, Justin R., Thompson, Craig B.·2020·Nature Immunology

DOI 10.1038/s41590-020-0725-2PMC PMC7442749

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Abstract

The majority of tumor-infiltrating T cells exhibit a terminally exhausted phenotype, marked by a loss of self-renewal capacity. How repetitive antigenic stimulation impairs T cell self-renewal remains poorly defined. Here, we show that persistent antigenic stimulation impaired ADP-coupled oxidative phosphorylation. The resultant bioenergetic compromise blocked proliferation by limiting nucleotide triphosphate synthesis. Inhibition of mitochondrial oxidative phosphorylation in activated T cells was sufficient to suppress proliferation and upregulate genes linked to T cell exhaustion. Conversely, prevention of mitochondrial oxidative stress during chronic T cell stimulation allowed sustained T cell proliferation and induced genes associated with stem-like progenitor T cells. As a result, antioxidant treatment enhanced the anti-tumor efficacy of chronically stimulated T cells. These data reveal that loss of ATP production through oxidative phosphorylation limits T cell proliferation and effector function during chronic antigenic stimulation. Furthermore, treatments that maintain redox balance promote T cell self-renewal and enhance anti-tumor immunity. Thompson and colleagues show that repetitive antigenic stimulation within the tumor environment triggers mitochondrial dysfunction by inhibiting oxidative phosphorylation, which leads to T cell exhaustion.

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Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Self-citation
The Molecular Signatures Database Hallmark Gene Set Collection
Liberzon, A., Birger, C., Thorvaldsdóttir, H., Ghandi, M., Mesirov, J. P., & Tamayo, P. (2015) · Cell Systems · doi:10.1016/j.cels.2015.12.004 · Cited by 13,807
On the origin of cancer cells
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
Cancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel III, E. E., Koeppen, H., Astarita, J. L., Cubas, R., et al. (2018) · Nature · doi:10.1038/nature25501 · Cited by 5,400
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Cellular response to oxidative stress: Signaling for suicide and survival*
Martindale, J. L., & Holbrook, N. J. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10119 · Cited by 2,314

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Riesenberg, B., Hunt, E. G., Tennant, M. D., Hurst, K. E., Andrews, A. M., Leddy, L. R., Neskey, D. M., Hill, E. G., Rivera, G. O. R., Paulos, C. M., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-1744 · Cited by 30
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Wang, Y., Liu, M., Zhang, L., Liu, X., Ji, H., Wang, Y., Gui, J., Yan, Y., & Wen, Z. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06336-4 · Cited by 31
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Li, J., Huang, C., Tang, P., Wu, R., Wu, Q., & Zhang, C. (2026) · Journal of Hematology & Oncology · doi:10.1186/s13045-026-01780-z · Cited by 34
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Levite, M. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.357903 · Cited by 29
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Hu, Y., Sarkar, A., Song, K., Michael, S., Höök, M., Wang, R., Heczey, A., & Song, X. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101530 · Cited by 30
Intracellular dehydrogenation catalysis leads to reductive stress and immunosuppression
Jiang, J., Zheng, H., Wang, Z., Wang, X., Xie, Q., Liu, X., Yang, Q. K., Cai, X., Gao, X., Li, R., et al. (2025) · Nature Nanotechnology · doi:10.1038/s41565-025-01870-y · Cited by 31
Harnessing Antioxidants in Cancer Therapy: Opportunities, Challenges, and Future Directions
Liu, Y., Wu, G., Feng, L., Li, J., Xia, Y., Guo, W., & Zhao, K. (2025) · Antioxidants · doi:10.3390/antiox14060674 · Cited by 32
Metabolic Control of Memory T-Cell Generation and StemnessPreprint
Raynor, J. L., Chapman, N. M., & Chi, H. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a037770 · Cited by 28
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Lawton, M. L., Inge, M. M., Blum, B. C., Smith-Mahoney, E. L., Bolzan, D., Lin, W., McConney, C., Porter, J., Moore, J., Youssef, A., et al. (2024) · PLoS Biology · doi:10.1371/journal.pbio.3002943 · Cited by 25
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Zhu, W., Li, Y., Han, M., & Jiang, J. (2023) · Biology · doi:10.3390/biology12040541 · Cited by 28
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Howard, E. D., Hurrell, B. P., Helou, D. G., Shafiei-Jahani, P., Hasiakos, S., Painter, J. D., Srikanth, S., Gwack, Y., & Akbari, O. (2023) · Nature Communications · doi:10.1038/s41467-023-41065-4 · Cited by 27
Potential mechanisms of cancer stem‐like progenitor T‐cell bio‐behaviours
Ni, L. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1817 · Cited by 26
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Song, J., Yi, X., Gao, R.-L., Sun, L., Wu, Z., Zhang, S., Huang, L., Han, C., & Ma, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.873834 · Cited by 29
Polymorphic KIR3DL3 expression modulates tissue-resident and innate-like T cells
Palmer, W. H., Leaton, L. A., Codo, A. C., Crute, B. W., Roest, J., Zhu, S., Petersen, J., Tobin, R. P., Hume, P. S., Stone, M. L., et al. (2023) · Science Immunology · doi:10.1126/sciimmunol.ade5343 · Cited by 24
Metabolic plasticity of T cell fate decision
Pan, X., Wang, J., Zhang, L., Li, G., & Huang, B. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002989 · Cited by 26
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Feng, D., Pu, D., Ren, J., Liu, M., Zhang, Z., Liu, Z., & Li, J. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189193 · Cited by 26
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Tejero, J. D., Hesterberg, R. S., Drápela, S., Ilter, D., Raizada, D., Lazure, F., Kashfi, H., Liu, M., Silvane, L., Avram, D., et al. (2024) · Oncogene · doi:10.1038/s41388-024-03191-1 · Cited by 26
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Jenkins, Y. R., Zabkiewicz, J., Ottmann, O. G., & Jones, N. (2021) · Antibodies · doi:10.3390/antib10020017 · Cited by 24
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Zhao, J., Wang, Z., Tian, Y., Ning, J., & Ye, H. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.07.001 · Cited by 26
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Zhu, Z., Luo, Y., Lou, G., Yihunie, K. D., Wizzard, S., DeVilbiss, A., Muh, S., Ma, C., Shinde, S. S., Hoar, J., et al. (2024) · Science Immunology · doi:10.1126/sciimmunol.adk2954 · Cited by 25
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Dahabieh, M. S., DeCamp, L. M., Oswald, B. M., Kitchen-Goosen, S. M., Fu, Z. F., Vos, M., Compton, S. E., Longo, J., Foy, N. M., Williams, K. S., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02185-9 · Cited by 24
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Zhang, Y., Li, W., Bian, Y., Li, Y., & Cong, L. (2023) · PeerJ · doi:10.7717/peerj.14797 · Cited by 27
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Heaton, A. R., Rehani, P. R., Hoefges, A., Lopez, A. F., Erbe, A. K., Sondel, P. M., & Skala, M. C. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1110503 · Cited by 23
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Wilson, J. J., Wei, J. Q., Daamen, A. R., Sears, J. D., Bechtel, E., Mayberry, C. L., Stafford, G. A., Bechtold, L. S., Grammer, A. C., Lipsky, P. E., et al. (2023) · iScience · doi:10.1016/j.isci.2023.107487 · Cited by 24
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Zhu, Y., Tan, H., Wang, J., Zhuang, H., Zhao, H., & Lu, X. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107161 · Cited by 28
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de Assis, P. A., Allen, R., Schaller, M. A., Kunkel, S. L., & Bermick, J. (2024) · iScience · doi:10.1016/j.isci.2024.110114 · Cited by 23
Transcriptional reprogramming primes CD8+ T cells toward exhaustion in Myalgic encephalomyelitis/chronic fatigue syndrome
Iu, D. S. H., Maya, J., Vu, L. T., Fogarty, E. A., McNairn, A. J., Ahmed, F., Franconi, C. J., Munn, P. R., Grenier, J. K., Hanson, M. R., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2415119121 · Cited by 22

Authors: Vardhana, S. A., Hwee, M. A., Berisa, M., Wells, D. K., Yost, K. E., King, B., Smith, M., Herrera, P. S., Chang, H. Y., Satpathy, A. T., van den Brink, M. R. M., Cross, J. R., & Thompson, C. B.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Parker Institute for Cancer Immunotherapy (US)
Stanford Medicine (US)
Howard Hughes Medical Institute (US)
Corresponding author: Thompson, Craig B.
ORCID: Vardhana, Santosha A.
Berisa, Mirela
Wells, Daniel K.
Yost, Kathryn E.
King, Bryan
Smith, Melody
Chang, Howard Y.
Satpathy, Ansuman T.
Cross, Justin R.
Thompson, Craig B.
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2020-07-13
Volume: 21
Issue: 9
Pages: 1022-1033
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/s41590-020-0725-2
PMC: PMC7442749
OpenAlex: W3040911066
Semantic Scholar: 0e26544b84036d0da9a73a3a38337fc7b1573819
Cited by: 575
References: 67
Citations by year: 2026: 133 · 2025: 117 · 2024: 112 · 2023: 90 · 2022: 68 · 2021: 46 · 2020: 9
FWCI: 18.62
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health (1r01hl147584-01a1)
National Heart, Lung, and Blood Institute (R01‐HL147584)
National Cancer Institute (K08CA237731, P30CA008748)
National Institute of Allergy and Infectious Diseases (R25AI140472)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: T cell exhaustion, mitochondrial oxidative phosphorylation, T cell self-renewal, chronic antigenic stimulation, T cell proliferation, mitochondrial oxidative stress, antioxidant treatment, redox homeostasis, tumor-infiltrating T cells, antitumor immunity
MeSH terms: Cell Self Renewal, Adenosine Diphosphate, Animals, Antigens, Neoplasm, Antioxidants, Energy Metabolism, Immune Tolerance, Lymphocyte Activation, Melanoma, Experimental, Mice, Inbred C57BL, Mitochondria, Neoplasms, Oxidative Phosphorylation, Lymphocytes, Tumor-Infiltrating, Clonal Anergy, CD8-Positive T-Lymphocytes, Cell Proliferation, Mice

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Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen

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