5-Fluorouracil Selectively Kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell–Dependent Antitumor Immunity
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Abstract
Myeloid-derived suppressor cells (MDSC) accumulate in the spleen and tumor bed during tumor growth. They contribute to the immune tolerance of cancer notably by inhibiting the function of CD8(+) T cells. Thus, their elimination may hamper tumor growth by enhancing antitumor T-cell functions. We have previously reported that some anticancer agents relied on T cell–dependent anticancer responses to achieve maximal efficacy. However, the effect of anticancer agents on MDSC has remained largely unexplored. In this study, we observed that gemcitabine and 5-fluorouracil (5FU) were selectively cytotoxic on MDSC. In vivo, the treatment of tumor-bearing mice with 5FU led to a major decrease in the number of MDSC in the spleens and tumor beds of animals whereas no significant effect on T cells, natural killer cells, dendritic cells, or B cells was noted. Interestingly, 5FU showed a stronger efficacy over gemcitabine to deplete MDSC and selectively induced MDSC apoptotic cell death in vitro and in vivo. The elimination of MDSC by 5FU increased IFN-γ production by tumor-specific CD8(+) T cells infiltrating the tumor and promoted T cell–dependent antitumor responses in vivo. Altogether, these findings suggest that the antitumor effect of 5FU is mediated, at least in part, by its selective cytotoxic action on MDSC. Cancer Res; 70(8); 3052–61. ©2010 AACR.
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5-fluorouracil, doxorubicin, gemcitabine, and docetaxel reduced circulating myeloid-derived suppressor cells (MDSCs) in mouse models.
“although 5-fluorouracil, doxorubicin, gemcitabine, and docetaxel reduced circulating myeloid-derived suppressor cells (MDSCs) in mouse models [42–45]”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [42]
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- Authors
- Vincent, J., Mignot, G., Chalmin, F., Ladoire, S., Bruchard, M., Chevriaux, A., Martin, F., Apetoh, L., Rébé, C., & Ghiringhelli, F.
- Affiliations
- Brigham and Women's Hospital (US)
- Authors' Affiliations: 1INSERM Research Center 866, AVENIR Team; 2Faculty of Medicine, University of Burgundy, 3Anti-Cancer Center, Georges François Leclerc, Dijon, France; and 4Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- ORCID
- Venue
- Cancer Research
- Published
- 2010-04-14
- Volume
- 70
- Issue
- 8
- Pages
- 3052-3061
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2079068389
- Cited by
- 1,245
- References
- 39
- Citations by year
- 2026: 49 · 2025: 64 · 2024: 67 · 2023: 81 · 2022: 106 · 2021: 122 · 2020: 117 · 2019: 81 · 2018: 80 · 2017: 67 · 2016: 97 · 2015: 74 · 2014: 67 · 2013: 63 · 2012: 47
- FWCI
- 23.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- 5-fluorouracil, myeloid-derived suppressor cells, gemcitabine, selective cytotoxicity, CD8+ T cells, antitumor immunity, interferon-gamma, tumor immunosuppression, spleen, tumor microenvironment
- MeSH terms
- Gemcitabine, Animals, Antimetabolites, Antineoplastic, Dendritic Cells, Deoxycytidine, Flow Cytometry, Fluorouracil, Immune System, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Neoplasm Transplantation, T-Lymphocytes, Apoptosis, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Mice
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