Regulatory T cells in cancer immunotherapy
Open accessAbstract
FOXP3-expressing regulatory T (Treg) cells, which suppress aberrant immune response against self-antigens, also suppress anti-tumor immune response. Infiltration of a large number of Treg cells into tumor tissues is often associated with poor prognosis. There is accumulating evidence that the removal of Treg cells is able to evoke and enhance anti-tumor immune response. However, systemic depletion of Treg cells may concurrently elicit deleterious autoimmunity. One strategy for evoking effective tumor immunity without autoimmunity is to specifically target terminally differentiated effector Treg cells rather than all FOXP3+ T cells, because effector Treg cells are the predominant cell type in tumor tissues. Various cell surface molecules, including chemokine receptors such as CCR4, that are specifically expressed by effector Treg cells can be the candidates for depleting effector Treg cells by specific cell-depleting monoclonal antibodies. In addition, other immunological characteristics of effector Treg cells, such as their high expression of CTLA-4, active proliferation, and apoptosis-prone tendency, can be exploited to control specifically their functions. For example, anti-CTLA-4 antibody may kill effector Treg cells or attenuate their suppressive activity. It is hoped that combination of Treg-cell targeting (e.g., by reducing Treg cells or attenuating their suppressive activity in tumor tissues) with the activation of tumor-specific effector T cells (e.g., by cancer vaccine or immune checkpoint blockade) will make the current cancer immunotherapy more effective.
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The aTregs identified are reminiscent of Tregs with enhanced suppression activity previously observed within tumors of patients with solid cancers.
“The aTregs we identified are thus reminiscent of Tregs with enhanced suppression activity previously observed within tumors of patients with solid cancers (55).”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [55]
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- Authors
- Tanaka, A., & Sakaguchi, S.
- Affiliations
- Immunology Frontier Research Center, The University of Osaka (JP)
- Corresponding author
- Sakaguchi, Shimon
- Venue
- Cell Research
- Published
- 2016-12-20
- Volume
- 27
- Issue
- 1
- Pages
- 109-118
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- PMC
- PMC5223231
- OpenAlex
- W2561926137
- Cited by
- 1,860
- References
- 90
- Citations by year
- 2026: 113 · 2025: 198 · 2024: 315 · 2023: 275 · 2022: 274 · 2021: 207 · 2020: 154 · 2019: 144 · 2018: 126 · 2017: 52 · 2016: 1 · 2014: 1
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (16H06295, 17K15723)
- 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
- regulatory T cells, Foxp3, cancer immunotherapy, antitumor immunity, effector regulatory T cells, Treg depletion, autoimmunity, CCR4, CTLA-4, anti-CTLA-4 antibody, tumor-infiltrating Treg cells, immune checkpoint blockade, cancer vaccines, Treg suppressive function
- MeSH terms
- Animals, Humans, Immunity, Immunotherapy, Neoplasms, Lymphocytes, Tumor-Infiltrating, Models, Immunological, T-Lymphocytes, Regulatory
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