Immunoregulation by resveratrol; implications for normal tissue protection and tumour suppression

Armineh Rezagholi Lalani, Fatemeh Fakhari, Shakila Radgoudarzi, Nima Rastegar‐Pouyani, Kave Moloudi, Ehsan Khodamoradi, Shahram Taeb, Masoud Najafi

Immune reactions are involved in both tumor and normal tissue in response to therapy. Elevated secretion of certain chemokines, exosomes, and cytokines triggers inflammation, pain, fibrosis, and ulceration among other normal tissue side effects. On the other hand, secretion of tumor-promoting molecules suppresses activity of anticancer immune cells and facilitates the proliferation of malignant cells. Novel anticancer drugs such as immune checkpoint inhibitors (ICIs) boost anticancer immunity via inducing the proliferation of anticancer cells such as natural killer (NK) cells and CD8+ T lymphocytes. Certain chemotherapy drugs and radiotherapy may induce anticancer immunity in the tumor, however, both of which have severe side effects for normal tissues through stimulation of several immune responses. Thus, administration of natural products with low side effects may be a promising approach to modulate the immune system in both tumor and normal organs. Resveratrol is a well-known phenol with diverse effects on normal tissues and tumors. To date, a large number of experiments have confirmed the potential of resveratrol as an anticancer adjuvant. This review focuses on ensuing stimulation or suppression of immune responses in both tumor and normal tissue after radiotherapy or anticancer drugs. Later on, the immunoregulatory effects of resveratrol in both tumor and normal tissue following exposure to anticancer agents will be discussed. This article is protected by copyright. All rights reserved.