The Triad, Hypoxia–ROS–Inflammation

Abstract

Growing tumor is dynamic mixture of altered cells, immune cells as well as tumor-associated normal tissue cells, and together the microenvironment dynamics is both extremely complex and fast transforming. Density of cells, composition of primary site of tumor, elasticity, and local tissue metabolism all contribute how a certain tumor at a particular tissue or organ will develop making the tumor such a diverse and complicated group of diseases that are often not controllable via existing therapeutic modalities. Oxidative stress due to tumor cells owns metabolic peculiarities as well as adjustor cells such as macrophages, and proinflammatory cells such as neutrophil further contribute to the situation (Bhattacharyya and Saha 2015). Moreover, infiltrating immune cells secrete inflammation mediator, suppress or kill antitumor T cells, and when tumor cell number reaches a certain threshold, tumor environment starts to get hypoxic that not only fuels further increase in reactive oxygen and nitrogen mediators but also damages T cell immunity and alters tumor-associated immune cells (Saha et al. 2020). Right now, we are witnessing the dawn of the immunotherapy with tools such as cancer-specific chimeric antigen receptor (CAR) T cell which is becoming more easily accessible; to keep the microenvironment factors as for any T-cell-based immunotherapy successful, the suppressive inflammatory tumor microenvironment has to be regulated and converted toward more T-cell-friendly condition.