Cited by 215Cancer, Hypoxia, and MetabolismImmune cells in cancerCancer Immunotherapy and Biomarkers

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Molecular Pathways: Hypoxia Response in Immune Cells Fighting or Promoting Cancer

Palazón, Asis, Aragonés, Julián, Morales-Kastresana, Aizea, de Landázuri, Manuel Ortiz, Melero, Ignacio·2012·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-11-1591

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Abstract

Both malignant and stromal components in tumors are influenced by the physiologic conditions of the microenvironment. Hypoxia is a prominent feature of solid tumors as a result of defective vascularization and intense metabolic activity. The gene-expression control mechanisms that adapt tissues to hypoxia are exploited by tumors to promote angiogenesis and vasculogenesis. The functions of infiltrating immune cells (macrophages and lymphocytes) and other stromal components are also influenced by a limited O(2) supply. Hypoxia-inducible factors (HIF) are the main molecular transcriptional mediators in the hypoxia response. The degradation and activity of HIF-1α and HIF-2α are tightly controlled by the fine-tuned action of oxygen-sensing prolyl and asparaginyl hydroxylase enzymes. Recent evidence indicates that hypoxia can modulate the differentiation and function of T lymphocytes and myeloid cells, skewing their cytokine-production profiles and modifying the expression of costimulatory receptors. This conceivably includes tumor-infiltrating lymphocytes. Hypoxia not only directly affects tumor-infiltrating leukocytes but also exerts effects on tumor cells and vascular cells that indirectly cause selective chemokine-mediated recruitment of suppressive and proangiogenic T-cell subsets. This review focuses on changes induced by hypoxia in immune cells infiltrating solid malignancies. Such changes may either promote or fight cancer, and thus are important for immunotherapy.

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Authors: Palazón, A., Aragonés, J., Morales-Kastresana, A., de Landázuri, M. O., & Melero, I.
Affiliations: Authors' Affiliations: 1Center for Applied Medical Research, University of Navarra, and 2Servicio de Oncología, Clinica Universidad de Navarra, Pamplona, Spain; 3Servicio de Inmunologia, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain
Hospital Universitario de La Princesa (ES)
Corresponding author: Melero, Ignacio
ORCID: Aragonés, Julián
Melero, Ignacio
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2012-03-01
Volume: 18
Issue: 5
Pages: 1207-1213
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-11-1591
OpenAlex: W2108984461
Cited by: 214
References: 66
Citations by year: 2026: 1 · 2025: 11 · 2024: 8 · 2023: 14 · 2022: 13 · 2021: 20 · 2020: 24 · 2019: 8 · 2018: 16 · 2017: 16 · 2016: 24 · 2015: 14 · 2014: 23 · 2013: 16 · 2012: 6
FWCI: 1.04
Type: journal article
Language: en
Open access: closed
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: tumor hypoxia, hypoxia-inducible factor, HIF-1α, HIF-2α, oxygen sensing, prolyl hydroxylase, asparaginyl hydroxylase, tumor microenvironment, tumor-infiltrating lymphocytes, tumor-associated macrophages, T cell differentiation, tumor angiogenesis, tumor stroma, cancer immunotherapy
MeSH terms: Animals, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Signal Transduction, Cell Hypoxia, Lymphocytes, Tumor-Infiltrating, Translational Research, Biomedical

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Molecular Pathways: Hypoxia Response in Immune Cells Fighting or Promoting Cancer

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