Journal
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
Volume 10, Issue 1, Pages 19-30Publisher
EXPERT REVIEWS
DOI: 10.1586/1744666X.2014.865520
Keywords
5-fluorouracil; anticancer immunity; inflammasome; immunomodulation; immunosuppression; myeloid-derived suppressor cell
Categories
Funding
- Ligue Nationale Contre le Cancer
- Fondation de France
- Institut National du Cancer
- Association pour la recherche sur le cancer
- Conseil Regional de Bourgogne
- FEDER
- Agence Nationale de la Recherche [ANR-10-PDOC-014-01]
- Ligue Regionale contre le cancer Comite Grand-Est
- European Community (Marie Curie Fellowship) [PCIG10-GA-2011-303719]
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Preclinical studies have revealed an unexpected ability of the immune system to contribute to the success of chemotherapy and radiotherapy. Anticancer therapies can trigger immune system activation by promoting the release of danger signals from dying tumor cells and/or the elimination of immunosuppressive cells. We have, however, recently discovered that some chemotherapies, such as 5-fluorouracil and gemcitabine, exert conflicting effects on anticancer immune responses. Although 5-fluorouracil and Gem selectively eliminated myeloid-derived suppressive cells in tumor-bearing rodents, these chemotherapies promoted the release of IL-1 beta and the development of pro-angiogenic IL-17-producing CD4 T cells. The ambivalent effects of chemotherapy on immune responses should thus be carefully considered to design effective combination therapies based on chemotherapy and immune modulators. Herein, we discuss how the initial findings underscoring the key role of the immune system in mediating the antitumor efficacy of anticancer agents could begin to translate into effective therapies in humans.
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