Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation

Abstract

Tumor microenvironment (TME) is composed of diverse cell types whose interactions, both direct and indirect, significantly influence tumorigenesis and therapeutic outcomes. Within TME, reactive oxygen species (ROS) are produced by various cells and exhibit a dual role: moderate ROS levels promote tumor initiation and progression, whereas excessive levels induce cancer cell death, influencing the efficacy of anticancer therapies. Inflammasomes, cytosolic multiprotein complexes, are pivotal in multiple stages of tumorigenesis and play a crucial role in establishing the inflammatory TME. By releasing cytokines such as IL-1β and IL-18, inflammasomes contribute to immune cell recruitment and sustain a chronic inflammatory state that supports tumor growth. ROS are critical regulators of inflammasome activation, with the impact of ROS-mediated activation differing across cell types, leading to distinct influences on tumor progression and therapeutic responses. This review explores how ROS drive inflammasome activation in various TME-associated cells and the reciprocal ROS generation induced by inflammasomes, examining their multifaceted impact on tumorigenesis and therapeutic efficacy. By elucidating the complex interplay between ROS and inflammasomes in TME, we provide insights into potential therapeutic approaches that could modulate cancer progression and enhance treatment outcomes.

Keywords: IL-1β; Inflammasome; Reactive oxygen species; Tumor microenvironment.