Tumor immunomodulatory effects of polyphenols

Abstract

Polyphenols, commonly found in various plants, have attracted enormous attention due to their potential pharmacological activity, especially antitumor activity dependent on immune function. In recent years, the development of nanomedicine can counteract the low bioavailability of polyphenols and improve the effect of tumor treatment. Among them, metal-phenolic networks (MPNs), which utilize various metal ions and phenolic ligands for coordination binding, have now become candidates for polyphenol-based nanomedicine treatment of tumors. In this mini-review, we described the classification of polyphenols and their mechanisms in antitumor immune responses, and provided suggestions for the next steps of treating tumors with polyphenols.

Keywords: MPNs; bioavailability; natural compounds; polyphenols; tumor immunity.

Figure 1

The basic classification of common polyphenols.

Figure 2

Regulation of immune cells in the tumor microenvironment: NK cells represent the first line of defense against a tumor cell. Immunogenic cell death increases the expression of costimulatory molecules (CD80/86) by APCs. Tumor peptide presentation to T cells leads to subsequent activation. CD8+ T cell-mediated elimination of tumor cells occurs via MHC-I recognition. Cytokines from T helper cells enhance the activity of macrophages and NK cells. MDSCs can also create the immunosuppressive cytokines that prevent CTLs and T_H cells from attacking tumors.

Figure 3

Regulation effects of polyphenols on immune cells: polyphenols can enhance NK cell antitumor activity. Some polyphenols can also induce immature MDSCs to differentiate into other mature immune cells. Polyphenols can inhibit the M2-like polarization of TAMs and enhancement the polarization of macrophages toward the M1 phenotype, which exerts antitumor effects. Polyphenols induce immunogenic cell death and induce cellular immunity by activating T_H1 responses. Various polyphenols such as EGCG, genistein, and resveratrol can enhance the number and activities of CTLs. Bisdemethoxycurcumin decreases the level of PD-1 expression on the surface of CD8+ T lymphocytes, thus enhancing the CTLs’ cytotoxically activity and immune surveillance. In addition, Polyphenols induce tumor immunity by inhibiting the function of Treg and shifting from a T_H2 or Treg balance to a T_H1 response against the tumoral antigen.