Tumour, Oxidative Stress and Host T Cell Response: Cementing the Dominance.

Abstract

Reactive oxygen species (ROS) and free radicals are produced intrinsically during normal cellular metabolic processes or extrinsically due to ionizing radiations, UV rays, xenobiotic insult, etc. ROS are important signal mediators and are used by the immune system to destroy pathogens, but as these are highly reactive, they also have the capacity to cause DNA damage and alter protein and lipid components of a cell. As a result, cells have evolved a tight regulation of internal redox environment that involves a balanced interplay between free radicals produced and quenched by cellular antioxidants and enzyme systems. Any deregulation of this subtle balance can result in oxidative stress that can lead to various pathological conditions including cancer. Oxidative stress can be a cause of neoplasia, or it can be induced by a growing tumour itself. The link existing between oxidative stress and inflammation is also very strong. Suppressed cellular immune system, especially effector T cell system, is a characteristic of tumour-bearing host. Both the direct oxidative stress caused by tumour cell(s) and oxidative stress mediators present in tumour microenvironment play a significant role in the suppression of effector T cell function and induction of T cell death. This review discusses in detail the complex interplay between tumour-stroma-immune system in the light of oxidative stress that dominates every phase of cancer including initiation, progression and establishment. This review also addresses in detail the mechanisms of oxidative stress-induced T cell dysfunction in tumour-bearing host and also briefly points out the possible therapeutic interventions.