Tumor Hypoxia Regulates Immune Escape/Invasion: Influence on Angiogenesis and Potential Impact of Hypoxic Biomarkers on Cancer Therapies.

Raefa Abou Khouzam,Klaudia Brodaczewska,Stephanie Buart,Salem Chouaib,Claudine Kieda,Aleksandra Filipiak,Nagwa Ahmed Zeinelabdin,Cezary Szczylik

doi:10.3389/fimmu.2020.613114

Abstract

The environmental and metabolic pressures in the tumor microenvironment (TME) play a key role in molding tumor development by impacting the stromal and immune cell fractions, TME composition and activation. Hypoxia triggers a cascade of events that promote tumor growth, enhance resistance to the anti-tumor immune response and instigate tumor angiogenesis. During growth, the developing angiogenesis is pathological and gives rise to a haphazardly shaped and leaky tumor vasculature with abnormal properties. Accordingly, aberrantly vascularized TME induces immunosuppression and maintains a continuous hypoxic state. Normalizing the tumor vasculature to restore its vascular integrity, should hence enhance tumor perfusion, relieving hypoxia, and reshaping anti-tumor immunity. Emerging vascular normalization strategies have a great potential in achieving a stable normalization, resulting in mature and functional blood vessels that alleviate tumor hypoxia. Biomarkers enabling the detection and monitoring of tumor hypoxia could be highly advantageous in aiding the translation of novel normalization strategies to clinical application, alone, or in combination with other treatment modalities, such as immunotherapy.

Highlights

The tumor microenvironment is a complex system, playing an important role in tumor development and progression
As antiangiogenic treatments have shown that destruction of angiogenesis leads to deep hypoxia and induces tumor resistance [7], efforts are focusing on rendering the tumor vessels functional to help treat the tumor [8, 9]
A challenge related to the hostility and complexity of the tumor microenvironment remains to be further elucidated to position immunotherapy as a transformative and the most used approach for the treatment of cancer

Summary

Introduction

The tumor microenvironment is a complex system, playing an important role in tumor development and progression. This aims to alleviate tumor hypoxia which would result in improvement of drug delivery, induction of an efficient anti-tumor immune response, and inhibition of cancer stem cells differentiation [100].

Results

Conclusion