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5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Vincent, Julie C. Mignot, Grégoire Chalmin, Fanny Ladoire, Sylvain Bruchard, Mélanie Chevriaux, Angélique Martin, François Apetoh, Lionel Rébé, Cédric Ghiringhelli, François |
| Copyright Year | 2010 |
| 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-gamma 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. |
| Starting Page | 1805 |
| Ending Page | 1810 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/70/8/3052.full.pdf |
| PubMed reference number | 20388795v1 |
| Alternate Webpage(s) | https://doi.org/10.1158/0008-5472.CAN-09-3690 |
| DOI | 10.1158/0008-5472.can-09-3690 |
| Journal | Cancer research |
| Volume Number | 70 |
| Issue Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Antineoplastic Agents Apoptosis Beds Cell Death Cell physiology Cellular Phone Excretory function Fluorouracil Immune Tolerance Infiltration Leukemia, B-Cell Neoplasms Recombinant Interferon-gamma Spleen Tissue T-Lymphocyte gemcitabine |
| Content Type | Text |
| Resource Type | Article |
