Bridging angiogenesis and immune evasion in the hypoxic tumor microenvironment.

Hypoxia (low O2) is a ubiquitous microenvironmental factor promoting cancer progression, metastasis, and mortality, owing to the ability of cancer cells to co-opt physiological angiogenic responses. Notwithstanding, the pathophysiological induction of angiogenesis results in an abnormal tumor vasculature, further aggravating hypoxia in a feedforward loop that limits the efficacy of molecular targeted therapies. Recent studies suggest that, besides their canonical roles, angiogenic factors promote a panoply of immunosuppressive effects in the tumor microenvironment. Therefore, intratumoral hypoxia emerges as a hitherto unrecognized mechanism evolutionarily repurposing angiogenic molecules as (patho)physiological immunomodulators. On the other hand, antiangiogenic therapies could be aimed at impeding both tumor growth and immunotolerance toward cancer cells, a beneficial effect that can be countered if hypoxia signaling pathways are left unchecked, leading to therapeutic failure. This review summarizes evidence supporting the hypothesis that hypoxia acts as a common pathophysiological mechanism of resistance to immunotherapeutic and antiangiogenic agents while proposing potential strategies to curtail resistance and mortality in patients bearing solid malignancies.

• Publication year

  2018

• Venue

  American Journal of Physiology. Regulatory Integrative and Comparative Physiology

• Publication date

  2018-12-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1152/ajpregu.00209.2018PMID 30183339
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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