Natural products and their derivatives: Promising modulators of tumor immunotherapy

Abstract

A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the anticancer activities of natural products and their derivatives. Increasing interest has been driven toward finding novel potential modulators of tumor immunotherapy from natural products, a hot research topic worldwide. These works of research mainly focused on natural products, including polyphenols (e.g., curcumin, resveratrol), cardiotonic steroids (e.g., bufalin and digoxin), terpenoids (e.g., paclitaxel and artemisinins), and polysaccharide extracts (e.g., lentinan). Compelling data highlight that natural products have a promising future in tumor immunotherapy. Considering the importance and significance of this topic, we initially discussed the integrated research progress of natural products and their derivatives, including target T cells, macrophages, B cells, NKs, regulatory T cells, myeloid-derived suppressor cells, inflammatory cytokines and chemokines, immunogenic cell death, and immune checkpoints. Furthermore, these natural compounds inactivate several key pathways, including NF-κB, PI3K/Akt, MAPK, and JAK/STAT pathways. Here, we performed a deep generalization, analysis, and summarization of the previous achievements, recent progress, and the bottlenecks in the development of natural products as tumor immunotherapy. We expect this review to provide some insight for guiding future research.

Keywords: Tregs; cardiotonic steroids; polyphenolics; polysaccharides; terpenoids; tumor immunotherapy.

FIGURE 1

The chemical structure of representative natural products

FIGURE 2

Proposed models for the molecular mechanisms of immunomodulatory effects by natural productions. Inhibitory effects of natural products on tumors through enhancing the cytotoxic function of effect T cells and NKs, attenuating CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs), reducing myeloid‐derived suppressor cells, decreasing TGF‐β, IL‐10, IL‐5, indoleamine 2,3‐dioxygenase, ARG1 levels, inducing IL‐12, IFN‐γ, and TNF‐α/β production, and preventing cell‐cell interaction of Tregs via the inhibition of CTLA‐4 and PD‐L1