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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 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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Yamaguchi, T., Kishi, A., Osaki, M., Morikawa, H., Martín, P. P., Wing, K., Saito, T., & Sakaguchi, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307185110 · Cited by 111
Self-citationLeonard A. Herzenberg 1931–2013
Nolan, G. P. (2013) · Nature Immunology · doi:10.1038/ni.2791 · Cited by 11
Pluto-bound probe faces crisis
Witze, A. (2014) · Nature · doi:10.1038/509407a · Cited by 5
Flagged first, then by citations
1 of the 90 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Zhang, Y., & Zhang, Z. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0488-6 · Cited by 2,906
Mao, X., Xu, J., Wang, W., Liang, C., Hua, J., Liu, J., Zhang, B., Meng, Q., Yu, X., & Shi, S. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01428-1 · Cited by 2,290
Roles of the immune system in cancer: From tumor initiation to metastatic progression
Gonzalez, H., Hagerling, C., & Werb, Z. (2018) · Genes & Development · doi:10.1101/gad.314617.118 · Cited by 2,111
Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment
Azizi, E., Carr, A. J., Plitas, G., Cornish, A. E., Konopacki, C., Prabhakaran, S., Nainys, J., Wu, K., Kiseliovas, V., Setty, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.060 · Cited by 1,976
Tumor microenvironment as a therapeutic target in cancer
Xiao, Y. Q., & Yu, D. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107753 · Cited by 2,026
Metadata
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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