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Cited by 3Cancer, Hypoxia, and MetabolismCancer Immunotherapy and BiomarkersImmune cells in cancer

Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review)

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Li, Chaoqun, Qin, Chenge, Li, Xingchen, Wang, Jinzhu, Li, Yang, Sun, Qin·2026·International Journal of Oncology
DOI 10.3892/ijo.2026.5845PMC PMC12823059
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Abstract

Hypoxic tumor microenvironment (TME) is a common occurrence in the development of solid tumors, which activates hypoxia‑inducible factors (HIFs) and their downstream signaling pathways in cancer cells to facilitate tumor progression and immune escape. However, among the various immune cells that constitute innate and adaptive immune systems, HIFs have a more intricate function; moreover, different isoforms of HIFs play different functions under spatial and temporal conditions. HIFs are conducive to the adaptation of various immune cells to the hypoxic TME. The stability of HIF‑α can regulate metabolism and directly regulate the expression of immune genes. Additionally, the activation of HIF signaling may also inhibit the development of immune cells in some tumor environments, affecting the antigen recognition and killing processes to assist cancer cells in immune escape. Therefore, understanding the relationship between HIF signaling and immune cells more comprehensively may yield substantial benefits for the immunotherapy of various types of cancer. The present study reviewed the role of HIFs in immunity, including their role in T cells, B cells, macrophages, neutrophils, dendritic cells and natural killer cells. It also discussed the effectiveness of HIF targeted therapy in clinical application, the challenges associated with it and the development of a precise targeting drug delivery system. The present review may help researchers comprehend the tumor immune process in a hypoxic microenvironment. It aimed to offer novel strategies for cancer immunotherapy and prolonging the overall survival of patients. .

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  • HIFs regulate immune cell metabolism and function, particularly in myeloid populations.

    “HIFs additionally regulate immune cell metabolism and function, particularly in myeloid populations [262,263].”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [263]

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Cited by

Sorted by citations

Authors
Li, C., Qin, C., Li, X., Wang, J., Li, Y., & Sun, Q.
Affiliations
  • Qufu Normal University (CN)
  • Tongji University (CN)
  • Qingdao Agricultural University (CN)
  • Center for The Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
  • Zhejiang Normal University (CN)
Corresponding author
Sun, Qin
ORCID
Venue
International Journal of Oncology
Publisher
Spandidos Publications
Published
2026-01-12
Volume
68
Issue
3
ISSN
  • 1019-6439 (ISSN-L)
  • 1791-2423
DOI
10.3892/ijo.2026.5845
PMC
PMC12823059
OpenAlex
W7124470898
Cited by
3
References
0
Citations by year
2026: 3
FWCI
2.53
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • International Journal of Oncology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
Funders
Natural Science Foundation of Shandong Province
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
hypoxia-inducible factor, tumor hypoxia, tumor-infiltrating immune cells, tumor immune evasion, cancer immunotherapy, HIF-targeted therapy, drug delivery systems, T cells, B cells, macrophages, neutrophils, dendritic cells, natural killer cells, cancer metabolism
MeSH terms
Animals, Humans, Immunotherapy, Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Lymphocytes, Tumor-Infiltrating, Tumor Escape, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Tumor Microenvironment

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