The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology
Open accessAbstract
Functional, tumor-specific CD8+ cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8+ effector T cell dysfunction. Among the many facets of CD8+ T cell dysfunction that have been recognized—tolerance, anergy, exhaustion, and senescence—CD8+ T cell senescence is incompletely understood. Naïve CD8+ T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8+CD28− senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8+CD28− senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8+ T cells could improve the efficacy of future anti-tumor immunotherapy.
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The T cell phenotype CD27−CD28−CD57+KLRG-1+ is an indicator of immunosenescence.
“Therefore, the T cell phenotype of CD27−CD28−CD57+KLRG-1+ is also an indicator of immunosenescence.”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [41]
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Immunosenescence and organoids: pathophysiology and therapeutic opportunities
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- Authors
- Huff, W. X., Kwon, J. H., Henriquez, M., Fetcko, K., & Dey, M.
- Affiliations
- Indiana University School of Medicine (US)
- University of Illinois Chicago (US)
- Corresponding author
- Dey, Mahua
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2019-06-08
- Volume
- 20
- Issue
- 11
- Pages
- 2810
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC6600236
- OpenAlex
- W2948362628
- Cited by
- 217
- References
- 191
- Citations by year
- 2026: 20 · 2025: 35 · 2024: 48 · 2023: 32 · 2022: 33 · 2021: 31 · 2020: 14 · 2019: 2 · 2018: 2
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc-nd)
- Purdue University Indianapolis (Indiana University) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- National Institutes of Health (K08NS092895)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- CD8+CD28- T cells, T cell senescence, CD8+ cytotoxic T lymphocytes, tumor microenvironment, immunosuppression, T cell exhaustion, regulatory T cells, costimulatory molecules, telomere damage, anti-tumor immunotherapy, aging
- MeSH terms
- Immunosenescence, Animals, Humans, Immunotherapy, Neoplasms, CD28 Antigens, CD8-Positive T-Lymphocytes
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