University of Oulu

Focaccetti, C., Izzi, V., Benvenuto, M., Fazi, S., Ciuffa, S., Giganti, M. G., … Bei, R. (2019). Polyphenols as Immunomodulatory Compounds in the Tumor Microenvironment: Friends or Foes? International Journal of Molecular Sciences, 20(7), 1714.

Polyphenols as immunomodulatory compounds in the tumor microenvironment : friends or foes?

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Author: Focaccetti, Chiara1; Izzi, Valerio2; Benvenuto, Monica1;
Organizations: 1Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
2Oulu Center for Cell-Matrix Research, University of Oulu, FIN-90014 Oulu, Finland
3Department of Experimental Medicine, University of Rome “Sapienza”, 00164 Rome, Italy
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2019
Publish Date: 2019-10-23


Polyphenols are natural antioxidant compounds ubiquitously found in plants and, thus, ever present in human nutrition (tea, wine, chocolate, fruits and vegetables are typical examples of polyphenol-rich foods). Widespread evidence indicate that polyphenols exert strong antioxidant, anti-inflammatory, anti-microbial and anti-cancer activities, and thus, they are generally regarded to as all-purpose beneficial nutraceuticals or supplements whose use can only have a positive influence on the body. A closer look to the large body of results of years of investigations, however, present a more complex scenario where polyphenols exert different and, sometimes, paradoxical effects depending on dose, target system and cell type and the biological status of the target cell. Particularly, the immunomodulatory potential of polyphenols presents two opposite faces to researchers trying to evaluate their usability in future cancer therapies: on one hand, these compounds could be beneficial suppressors of peri-tumoral inflammation that fuels cancer growth. On the other hand, they might suppress immunotherapeutic approaches and give rise to immunosuppressive cell clones that, in turn, would aid tumor growth and dissemination. In this review, we summarize knowledge of the immunomodulatory effects of polyphenols with a particular focus on cancer microenvironment and immunotherapy, highlighting conceptual pitfalls and delicate cell-specific effects in order to aid the design of future therapies involving polyphenols as chemoadjuvants.

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Series: International journal of molecular sciences
ISSN: 1661-6596
ISSN-E: 1422-0067
ISSN-L: 1661-6596
Volume: 20
Issue: 7
Article number: 1714
DOI: 10.3390/ijms20071714
Type of Publication: A2 Review article in a scientific journal
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This study was supported by a grant from the University of Rome “Tor Vergata” (Mission Sustainability, Codice Unico di Progetto (CUP): E81I18000330005).
Copyright information: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (