The role of hypoxia‐inducible factor 1 in tumor immune evasion

Abstract

Hypoxia‐inducible factor 1 (HIF‐1) plays an indispensable role in the hypoxic tumor microenvironment. Hypoxia and HIF‐1 are involved in multiple aspects of tumor progression, such as metastasis, angiogenesis, and immune evasion. In innate and adaptive immune systems, malignant tumor cells avoid their recognition and destruction by HIF‐1. Tumor immune evasion allows cancer cells to proliferate and metastasize and is associated with immunotherapy failure and chemoresistance. In the hypoxic tumor microenvironment, HIF‐1 signaling suppresses the innate and adaptive immune systems to evade immune attack by inducing the expression of immunosuppressive factors and immune checkpoint molecules, including vascular endothelial growth factor, prostaglandin E2, and programmed death‐ligand 1/programmed death‐1. Moreover, HIF‐1 blocks tumor‐associated antigen presentation via major histocompatibility complex class I chain‐related/natural killer group 2, member D signaling. Tumor‐associated autophagy and the release of tumor‐derived exosomes contribute to HIF‐1‐mediated immune evasion. This review focuses on recent findings on the potential mechanism(s) underlying the effect of hypoxia and HIF‐1 signaling on tumor immune evasion in the hypoxic tumor microenvironment. The effects of HIF‐1 on immune checkpoint molecules, immunosuppressive molecules, autophagy, and exosomes have been described. Additionally, the potential role of HIF‐1 in the regulation of tumor‐derived exosomes, as well as the roles of HIF‐1 and exosomes in tumor evasion, are discussed. This study will contribute to our understanding of HIF‐1‐mediated tumor immune evasion, leading to the development of effective HIF‐1‐targeting drugs and immunotherapies.

Development and Validation of a 7-Gene Prognostic Signature to Improve Survival Prediction in Pancreatic Ductal Adenocarcinoma

“…Multiple oncogenic pathways that were strongly associated with tumor progression, chemotherapeutic resistance, and immune cell infiltration were enriched. Biological processes and pathways, including but not limited to the PI3K-AKT signaling pathway, HIF-1 signaling pathway, and glycolysis, were all implicated in the regulation of malignant behavior and anticancer immunity (Xu et al, 2021b;Kobayashi et al, 2020;Sun and Meng, 2020;You et al, 2020). These findings could partly explain how the risk score affected patient survival and immune cell infiltration.…”

Hypoxia Constructing the Prognostic Model of Colorectal Adenocarcinoma and Related to the Immune Microenvironment

“…Currently, it has been reviewed that hypoxia induces immunosuppressive process by affecting immune cell transport and angiogenesis in the tumor microenvironment, and provides a basis for clinical monitoring (Augustin et al, 2020;Pietrobon and Marincola, 2021). More specifically, potential mechanisms by which HIF-1 signaling in the tumor microenvironment promotes immune escape and leads to poor prognosis include: induction of immunosuppressor and immune checkpoint molecule expression, autophagy, exosome release, and novel immunogenic cell death (Vito et al, 2020;You et al, 2020). Studies on COAD have shown that hypoxia promotes immunosuppression by inhibiting the differentiation of CD4 + effector T cells and enhancing the activity of regulatory T cells (Westendorf et al, 2017).…”

PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation

“…Transcriptional and growth factors are also implemented during oncogenesis via a modification of the immune response. Hypoxia-inducible factor 1 (HIF-1) plays an indispensable role in the hypoxic tumor microenvironment [9].…”