Hypoxia and the phenomenon of immune exclusion

Pietrobon, Violena; Marincola, Francesco M.

doi:10.1186/s12967-020-02667-4

Cited by 119Cancer Immunotherapy and BiomarkersCancer, Hypoxia, and MetabolismImmune cells in cancer

Hypoxia and the phenomenon of immune exclusion

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Pietrobon, Violena, Marincola, Francesco M.·2021·Journal of Translational Medicine

DOI 10.1186/s12967-020-02667-4PMC PMC7788724

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Abstract

Over the last few years, cancer immunotherapy experienced tremendous developments and it is nowadays considered a promising strategy against many types of cancer. However, the exclusion of lymphocytes from the tumor nest is a common phenomenon that limits the efficiency of immunotherapy in solid tumors. Despite several mechanisms proposed during the years to explain the immune excluded phenotype, at present, there is no integrated understanding about the role played by different models of immune exclusion in human cancers. Hypoxia is a hallmark of most solid tumors and, being a multifaceted and complex condition, shapes in a unique way the tumor microenvironment, affecting gene transcription and chromatin remodeling. In this review, we speculate about an upstream role for hypoxia as a common biological determinant of immune exclusion in solid tumors. We also discuss the current state of ex vivo and in vivo imaging of hypoxic determinants in relation to T cell distribution that could mechanisms of immune exclusion and discover functional-morphological tumor features that could support clinical monitoring.

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Hypoxia is a hallmark of most solid tumors and a common trait of the tumor microenvironment associated with cancer progression and metastasis.
“Hypoxia is a hallmark of most solid tumors and a common trait of TME that is associated with cancer progression and metastasis8–10.”
From Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy (2022) · cites this paper as [10]
Clinical studies have consistently demonstrated that hypoxia is associated with immune exclusion and resistance to immune checkpoint blockade therapy.
“clinical studies have consistently demonstrated that hypoxia is associated with immune exclusion and resistance to immune checkpoint blockade therapy10,20,21,51.”
From Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy (2022) · cites this paper as [10]

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[165]Wang Z, et al. Transglutaminase-2 of pancreatic cancer cells assembles a CXCL12-keratin 19-coat that mediates the resistance to immunotherapy. bioRxiv, 2019;2:776419.

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Authors: Pietrobon, V., & Marincola, F. M.
Affiliations: Refuge Biotechnologies (United States) (US)
Corresponding author: Pietrobon, Violena
ORCID: Pietrobon, Violena
Marincola, Francesco M.
Venue: Journal of Translational Medicine
Publisher: Springer Science and Business Media LLC
Published: 2021-01-06
Volume: 19
Issue: 1
Pages: 9-9
ISSN: 1479-5876 (ISSN-L)
DOI: 10.1186/s12967-020-02667-4
PMC: PMC7788724
OpenAlex: W3120650952
Cited by: 119
References: 467
Citations by year: 2026: 21 · 2025: 17 · 2024: 23 · 2023: 22 · 2022: 23 · 2021: 13
FWCI: 2.45
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Journal of Translational Medicine (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: tumor hypoxia, immune exclusion, solid tumors, tumor microenvironment, cancer immunotherapy, T cell distribution, chromatin remodeling, gene transcription, hypoxia imaging
MeSH terms: Hypoxia, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Cell Hypoxia, Tumor Microenvironment

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Hypoxia and the phenomenon of immune exclusion

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