Polyphenols as Immunomodulatory Compounds in the Tumor Microenvironment: Friends or Foes?

Abstract

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.

Nutrigenomic Effects of Long-Term Grape Pomace Supplementation in Dairy Cows

“…Several studies have shown how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms and/or inflammation antagonism. Further, polyphenols today represent also promising candidates for the therapy of autoimmune diseases [43][44][45][46].…”

“…All this was expected. Widespread evidence shows that polyphenols possess predominantly anti-oxidant, anti-inflammatory and immunomodulatory properties in both humans and farm animal species including cattle; hence, they are beneficial all-purpose nutraceuticals or supplements [45,46,88]. Polyphenols inhibit NF-κB, PI3K/Akt, MAPKs, and arachidonic acid-dependent signaling pathways.…”

“…Polyphenols inhibit NF-κB, PI3K/Akt, MAPKs, and arachidonic acid-dependent signaling pathways. Regarding their immunosuppressant properties, polyphenols modulate T-cell function (e.g., suppressing T helper 2 activation and promoting the development of regulatory T cells), inhibit mast cell degranulation, and downregulate inflammatory cytokine responses [45,46,76]. Owing to these immunomodulatory properties, polyphenols have emerged as potential tools for the treatment of autoimmune disorders [46,89].…”

Stability and anti-proliferative properties of biologically active compounds extracted from Cistus L. after sterilization treatments

“…Because glioblastoma tumors are chemotherapy-resistant with limited treatment options, investigation on new combination therapies or cancer immunotherapy has been prioritized by several research groups [47][48][49] . Recent evidence from numerous laboratories suggests that phytochemicals affect the immune response [50][51][52][53] . Gao et al 54 reported the effects of polyphenols on the development of several lymphocytic responses in vitro.…”

Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells

“…In studies where model antigens have been administered in animal models, it has been reported that curcumin supplementation increased T follicular helper cells and germinal centre B cells as well as subsequent IgG production [129]. The data on effects of polyphenols on immune cells is increasing, especially in the context of cancer [130], with a lot of research understandably focusing on the effects on Tregs [131]. Modulating this cell type is especially important for ovarian cancer [132][133][134].…”