Hypoxia as a Modulator of Inflammation and Immune Response in Cancer

SIMPLE SUMMARY: The tumoral microenvironment comprises cancer cells and surrounding components, including immune and endothelial cells, along with the extracellular matrix. As the tumoral cells proliferate, a gradient of oxygen and nutrients is established while the tumor becomes a solid mass. Tumoral cells have developed strategies to adapt themselves to the hypoxic microenvironment and to modify the tumoral microenvironment, including the inflammatory cells, in order to maintain their proliferation and ulterior metastasis, representing a crucial factor in the malignity of the disease. Therefore, we analyze the signaling and cellular components that interconnect inflammation and hypoxia, emphasizing the most recent findings and contributing to their understanding, as a reference for new therapeutic strategies. ABSTRACT: A clear association between hypoxia and cancer has heretofore been established; however, it has not been completely developed. In this sense, the understanding of the tumoral microenvironment is critical to dissect the complexity of cancer, including the reduction in oxygen distribution inside the tumoral mass, defined as tumoral hypoxia. Moreover, hypoxia not only influences the tumoral cells but also the surrounding cells, including those related to the inflammatory processes. In this review, we analyze the participation of HIF, NF-κB, and STAT signaling pathways as the main components that interconnect hypoxia and immune response and how they modulate tumoral growth. In addition, we closely examine the participation of the immune cells and how they are affected by hypoxia, the effects of the progression of cancer, and some innovative applications that take advantage of this knowledge, to suggest potential therapies. Therefore, we contribute to the understanding of the complexity of cancer to propose innovative therapeutic strategies in the future.