Phytochemicals as Immunomodulatory Molecules in Cancer Therapeutics

Abstract

Phytochemicals are natural plant-derived products that provide significant nutrition, essential biomolecules, and flavor as part of our diet. They have long been known to confer protection against several diseases via their anti-inflammatory, immune-regulatory, anti-microbial, and several other properties. Deciphering the role of phytochemicals in the prevention, inhibition, and treatment of cancer—unrestrained cell proliferation due to the loss of tight regulation on cell growth and replication—has been the focus of recent research. Particularly, the immunomodulatory role of phytochemicals, which is pivotal in unchecked cell proliferation and metastasis, has recently been studied extensively. The immune system is a critical component of the tumor microenvironment, and it plays essential roles in both preventing and promoting oncogenesis. Immunomodulation includes stimulation, amplification, or inactivation of some stage(s) of the immune response. Phytochemicals and their products have demonstrated immune regulation, such as macrophage migration, nitric oxide synthase inhibition, lymphocyte, T-cell, and cytokine stimulation, natural killer cell augmentation, and NFκB, TNF, and apoptosis regulation. There is a dearth of extensive accounts of the immunomodulatory effects of phytochemicals in cancer; thus, we have compiled these effects with mechanistic aspects of dietary phytochemicals in cancer, highlighting promising candidates and ongoing clinical trials on immunotherapeutic strategies to mitigate oncogenesis.

Echinacea purpurea root extract mitigates hepatotoxicity, genotoxicity, and ultrastructural changes induced by hexavalent chromium via oxidative stress suppression

“…Echinacea purpurea has promising antioxidant capabilities, the majority of which are linked to the high concentrations of bioactive phenolic components (Paudel et al 2023 ; Wojdylo et al 2007 ; Dogan et al 2014 ). However, there are few available findings on the beneficial influences of E. purpurea root extract in mammals.…”

“…Derivatives of caffeic acid particularly cichoric acid have a wide range of biological properties, inclusive of collagen protection, anti-hyaluronidase activity, antiviral activity, phagocyte activity promotion, and high antioxidant capacity (Barnes et al 2005 ; Bauer and Wagner 1991 ; Pellati et al 2004 ). Furthermore, E. purpurea possesses antifungal, antibacterial, anti-inflammatory, and anti-cancer activities (Paudel et al 2023 ; Kabir et al 2022 ; Hudson 2012 ; Gurley et al 2012 ). Numerous investigations have shown that E. purpurea extracts efficiently protect against liver damage brought on by alcohol, chemical pollutants, and obesity (Xiao et al 2013 ; Smalinskiene et al 2007 ; Landmann et al 2014 ).…”

A standardized combination of Terminalia chebula and Withania somnifera extracts enhances immune function in adults: a pilot randomized, double-blind, placebo-controlled clinical study

“…They have been used as adjuvant therapies in several conditions including cancer. Phytochemicals such as curcumin, allicin, alliin, and s-allyl cysteine have been shown to increase the ratio of CD4+/CD8+, enhance the production of IFN-γ in splenocyte of fibroblast tumors, and increase IFN-γ, IL-2 levels in breast cancer in Wistar rats ( 28 ). The efficacy of T. chebula is reported primarily due to the presence of phenolic compounds, which exhibit antioxidant and anti-inflammatory properties ( 29 ).…”

The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases

“…Phytochemicals, mostly polyphenols, are multitarget molecules, like metformin, and they affect many age-related signaling pathways. In fact, it is known that several phytochemicals possess immunomodulatory properties [ 181 ]. For instance, there is clear evidence that phytochemicals can improve the efficacy of many cancer therapies based on PD-1/PD-L1 blockade [ 182 , 183 ].…”