Emerging role of natural products in cancer immunotherapy

Abstract

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

Keywords: AKT, alpha-serine/threonine-specific protein kinase; Adoptive immune-cells transfer immunotherapy; B2M, beta-2-microglobulin; BMDCs, bone marrow dendritic cells; BPS, basil polysaccharide; BTLA, B- and T-lymphocyte attenuator; CAFs, cancer-associated fibroblasts; CCL22, C–C motif chemokine 22; CIKs, cytokine-induced killer cells; COX-2, cyclooxygenase-2; CRC, colorectal cancer; CTL, cytotoxic T cell; CTLA-4, cytotoxic T lymphocyte antigen-4; Cancer immunotherapy; Cancer vaccines; DAMPs, damage-associated molecular patterns; DCs, dendritic cells; FDA, US Food and Drug Administration; HCC, hepatocellular carcinoma; HER-2, human epidermal growth factor receptor-2; HIF-1α, hypoxia-inducible factor-1α; HMGB1, high-mobility group box 1; HSPs, heat shock proteins; ICD, Immunogenic cell death; ICTs, immunological checkpoints; IFN-γ, interferon γ; IL-10, interleukin-10; Immuno-check points; Immunosuppressive microenvironment; LLC, Lewis lung cancer; MDSCs, myeloid-derived suppressor cells; MHC, major histocompatibility complex class; MITF, melanogenesis associated transcription factor; MMP-9, matrix metalloprotein-9; Mcl-1, myeloid leukemia cell differentiation protein 1; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NKTs, natural killer T cells; NSCLC, non-small cell lung cancer; Natural products; OVA, ovalbumin; PD-1, programmed death-1; PD-L1, programmed death receptor ligand 1; PGE-2, prostaglandin E2; PI3K, phosphoinositide 3-kinase; ROS, reactive oxygen species; STAT3, signal transducer and activator of transcription 3; TAMs, tumor-associated macrophages; TAP, transporters related with antigen processing; TGF-β, transforming growth factor-β; TILs, tumor infiltration lymphocytes; TLR, Toll-like receptor; TNF-α, tumor necrosis factor α; TSA, tumor specific antigens; Teffs, effective T cells; Th1, T helper type 1; Tregs, regulatory T cells; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; mTOR, mechanistic target of rapamycin.