Tumor-induced senescent T cells with suppressor function: a potential form of tumor immune evasion
Open accessAbstract
Senescent and suppressor T cells are reported to be increased in select patients with cancer and are poor prognostic indicators. Based on the association of these T cells and poor outcomes, we hypothesized that tumors induce senescence in T cells, which negatively effects antitumor immunity. In this report, we show that human T cells from healthy donors incubated with tumor for only 6 h at a low tumor to T-cell ratio undergo a senescence-like phenotype, characterized by the loss of CD27 and CD28 expression and telomere shortening. Tumor-induced senescence of T cells is induced by soluble factors and triggers increases in expression of senescence-associated molecules such as p53, p21, and p16. Importantly, these T cells are not only phenotypically altered, but also functionally altered as they can suppress the proliferation of responder T cells. This suppression requires cell-to-cell contact and is mediated by senescent CD4+ and CD8+ subpopulations, which are distinct from classically described natural T regulatory cells. Our observations support the novel concept that tumor can induce senescent T cells with suppressor function and may effect both the diagnosis and treatment of cancer. [Cancer Res 2008;68(3):870–9]
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Tumor cells can induce T cell senescence in in vitro co-cultures.
“In line with this notion, tumor cells can induce T cell senescence in in vitro co-cultures [56].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [56]
Senescent CD8+ T lymphocytes aid tumor immune evasion by being functionally unresponsive and by suppressing responder T cells.
“Senescent CD8 + T lymphocytes not only contribute to tumor immune evasion through their functional unresponsiveness (42) and their suppressor function toward responder T cells (41,43)”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [41]
Soluble factors from tumors mediate senescence of T lymphocytes.
“Tumor-induced senescence of T lymphocytes is also mediated by tumor-derived soluble factors (41).”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [41]
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- Authors
- Montes, C. L., Chapoval, A. I., Nelson, J., Orhue, V., Zhang, X., Schulze, D. H., Strome, S. E., & Gastman, B. R.
- Affiliations
- 1Department of Otorhinolaryngology and
- University of Maryland, Baltimore (US)
- ORCID
- Venue
- Cancer Research
- Published
- 2008-02-01
- Volume
- 68
- Issue
- 3
- Pages
- 870-879
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W1979003707
- Cited by
- 127
- References
- 50
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 12 · 2023: 11 · 2022: 13 · 2021: 20 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 7 · 2012: 3
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- T cell senescence, regulatory T cells, tumor immune evasion, antitumor immunity, CD27, CD28, telomere shortening, p53, p21, p16, T cell proliferation inhibition, cell-cell contact, CD4+ T cells, CD8+ T cells, natural regulatory T cells
- MeSH terms
- Adult, DNA Damage, Humans, Lymphocyte Activation, Neoplasms, CD4-Positive T-Lymphocytes, Cellular Senescence, In Situ Hybridization, Fluorescence, CD8-Positive T-Lymphocytes, Cell Cycle Proteins, Tumor Escape, Jurkat Cells, Cell Line, Tumor, T-Lymphocytes, Regulatory
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