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Cited by 548T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmunotherapy and Immune Responses

Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy

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Kishton, Rigel J., Sukumar, Madhusudhanan, Restifo, Nicholas P.·2017·Cell Metabolism
DOI 10.1016/j.cmet.2017.06.016PMC PMC5543711
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Abstract

Cancer immunotherapy is an increasingly successful strategy for the treatment of patients who have advanced or conventional therapy-resistant cancers. T cells are key mediators of tumor destruction and their specificity for tumor-expressed antigens is of paramount importance, but other T cell-intrinsic qualities, such as durability, longevity, and functionality also play important roles in determining the efficacy of immunotherapy. The cellular energetic pathways that are utilized by T cells play a key role in regulating each of these qualities. Metabolic activity, which both regulates and is regulated by cellular signaling pathways and epigenetics, also profoundly influences the trajectories of T cell differentiation and fate. In this Review, we discuss how cell metabolism influences T cell anti-tumor activity, the metabolic qualities of highly-functional T cells, and strategies to modulate metabolism for improving the immune response to tumors.

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  • Aging is associated with alterations in mitochondrial function and mitochondrial dynamics in memory T cells.

    “The changes in the adaptive immune system, namely T-cells, with aging has been reported; memory T-cell function substantially decreases with aging (8,9), with alterations in mitochondrial function and mitochondrial dynamics (8–10).”

    From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [8]

    The sections on T cell longevity and in vitro metabolism link mitochondrial function and dynamics to memory T cell persistence and T cell activity. They do not establish that aging causes those mitochondrial alterations in memory T cells; the paper’s discussion of aging concerns cellular and organismal longevity more generally. Page numbers are not available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Memory T-cell function substantially decreases with aging.

    “The changes in the adaptive immune system, namely T-cells, with aging has been reported; memory T-cell function substantially decreases with aging (8,9), with alterations in mitochondrial function and mitochondrial dynamics (8–10).”

    From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [8]

    The sections on T-cell differentiation and metabolic activity discuss memory T-cell longevity and function, but do not say that memory T-cell function decreases with age. The section on metabolism and epigenetics discusses aging in cells and organisms generally, without making that connection. I searched for aging and age-related changes in memory T cells. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Kishton, R. J., Sukumar, M., & Restifo, N. P.
Affiliations
National Institutes of Health (US)
Corresponding author
  • Kishton, Rigel J.
  • Restifo, Nicholas P.
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2017-07
Volume
26
Issue
1
Pages
94-109
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2017.06.016
PMC
PMC5543711
OpenAlex
W2727838564
Cited by
548
References
22
Citations by year
2026: 42 · 2025: 69 · 2024: 81 · 2023: 89 · 2022: 81 · 2021: 76 · 2020: 67 · 2019: 27 · 2018: 13 · 2017: 3
FWCI
3.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Center for Cell-Based Therapy
  • NCI
  • NIH
  • NIH Center for Regenerative Medicine
  • Milstein Family Foundation
  • Intramural Research Program of the NCI (ZIA BC010763)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
T cell metabolism, T cell longevity, T cell function, cancer immunotherapy, antitumor immunity, T cell differentiation, metabolic reprogramming, epigenetics
MeSH terms
Animals, Cell Differentiation, Cell Survival, Humans, Immunity, Cellular, Immunotherapy, Neoplasms, T-Lymphocytes, Epigenesis, Genetic, Metabolic Networks and Pathways, Tumor Microenvironment

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