Mechanisms Behind Hypoxia-Driven Resistance to Immunotherapy in the Tumor Microenvironment

Abstract

Tumor formation requires rapid proliferation of malignant cells which consume large amounts of oxygen from the microenvironment to meet metabolic demands. The resulting tumor microenvironment (TME) is usually low in oxygen compared to healthy tissue and left in a hypoxic state. Immune cells in the tissue rely on oxygen for energy production, therefore immune function is often inhibited in the TME. Novel immunotherapy treatments aim to reinvigorate the immune system, thus making hypoxia a concrete barrier against immunotherapeutics targeting solid tumors. Furthermore, oxygen levels are highly variable dependent on the tissue, raising the question of the influence of physoxia on immune cell survival in hypoxic counterparts. This review aims to provide insight into the mechanisms that influence this question, using an in-silico approach, in order to understand how the field can improve immunotherapy treatments for patients.