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

Immune reactions are involved in both tumour 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 tumour‐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 tumour, however, both 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 tumour and normal organs. Resveratrol is a well‐known phenol with diverse effects on normal tissues and tumours. 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 tumour and normal tissue after radiotherapy or anticancer drugs. Later on, the immunoregulatory effects of resveratrol in both tumour and normal tissue following exposure to anticancer agents will be discussed. Damage‐associated molecular patterns (DAMPs) and reactive oxygen species (ROS) can trigger mitochondrial dysfunction and nuclear translocation of NF‐κB, leading to activation of NLRP3/inflammasome and release of pro‐inflammatory cytokines such as IL‐1. The release of growth factors and cytokines may cause fibrosis. These pathways are able to stimulate EMT and fibrosis. Resveratrol can blunt these pathways at different levels.