Normalization of the tumor microenvironment by harnessing vascular and immune modulation to achieve enhanced cancer therapy

Choi, Yechan; Jung, Keehoon

doi:10.1038/s12276-023-01114-w

Cited by 190Angiogenesis and VEGF in CancerCancer Immunotherapy and BiomarkersCancer Cells and Metastasis

Normalization of the tumor microenvironment by harnessing vascular and immune modulation to achieve enhanced cancer therapy

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Choi, Yechan, Jung, Keehoon·2023·Experimental & Molecular Medicine

DOI 10.1038/s12276-023-01114-wPMC PMC10689787

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Abstract

Solid tumors are complex entities that actively shape their microenvironment to create a supportive environment for their own growth. Angiogenesis and immune suppression are two key characteristics of this tumor microenvironment. Despite attempts to deplete tumor blood vessels using antiangiogenic drugs, extensive vessel pruning has shown limited efficacy. Instead, a targeted approach involving the judicious use of drugs at specific time points can normalize the function and structure of tumor vessels, leading to improved outcomes when combined with other anticancer therapies. Additionally, normalizing the immune microenvironment by suppressing immunosuppressive cells and activating immunostimulatory cells has shown promise in suppressing tumor growth and improving overall survival. Based on these findings, many studies have been conducted to normalize each component of the tumor microenvironment, leading to the development of a variety of strategies. In this review, we provide an overview of the concepts of vascular and immune normalization and discuss some of the strategies employed to achieve these goals.

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Various immunotherapeutic strategies have emerged, including adoptive cell transfer, primarily utilizing genetically modified T cells expressing chimeric antigen receptors (CAR T-cells), and adjuvant therapies such as dendritic cell, mRNA, and peptide-based vaccinations, which have the potential to convert 'cold' tumors into immunogenic 'hot' tumors by generating potent cytotoxic T lymphocyte (CTL
“To address this, various immunotherapeutic strategies have emerged, including adoptive cell transfer, primarily utilizing genetically modified T cells expressing chimeric antigen receptors (CAR T-cells) to recognize and eliminate cancer cells directly (Sterner and Sterner, 2021). Adjuvant therapies, such as dendritic cell, mRNA, and peptide-based vaccinations, aim to boost the patient’s anticancer”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Choi and Jung, 2023
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The vasculature in tumors exhibits structural disorganization and functional abnormalities, particularly in 'cold' tumors.
“The vasculature in tumors exhibits structural disorganization and functional abnormalities, particularly in ‘cold’ tumors (Choi and Jung, 2023).”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Choi and Jung, 2023
The Vascular normalization > Background section describes tumor vessels as irregular, leaky, and poorly perfused, supporting the structural and functional abnormalities. It does not say these abnormalities are particularly characteristic of ‘cold’ tumors; the only exact mention of cold tumors found is in a reference title. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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Authors: Choi, Y., & Jung, K.
Affiliations: Seoul National University (KR)
Corresponding author: Jung, Keehoon
ORCID: Jung, Keehoon
Venue: Experimental & Molecular Medicine
Publisher: Springer Science and Business Media LLC
Published: 2023-11-01
Volume: 55
Issue: 11
Pages: 2308-2319
ISSN: 1226-3613 (ISSN-L)
2092-6413
DOI: 10.1038/s12276-023-01114-w
PMC: PMC10689787
OpenAlex: W4388081006
Cited by: 188
References: 172
Citations by year: 2026: 109 · 2025: 47 · 2024: 32
FWCI: 4.97
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: Experimental & Molecular Medicine (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Research Foundation
Seoul National University
National Research Foundation of Korea (2021M3A9I4026318, NRF-2021M3A9I4026318)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: tumor microenvironment, tumor vasculature normalization, angiogenesis, anti-angiogenic therapy, immunosuppression, combination cancer therapy
MeSH terms: Humans, Immunotherapy, Neoplasms, Neovascularization, Pathologic, Angiogenesis Inhibitors, Tumor Microenvironment

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Normalization of the tumor microenvironment by harnessing vascular and immune modulation to achieve enhanced cancer therapy

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