Immunosuppressive networks in the tumour environment and their therapeutic relevance

Zou, Weiping

doi:10.1038/nrc1586

Cited by 2,057Cancer Immunotherapy and BiomarkersImmune cells in cancerT-cell and B-cell Immunology

Immunosuppressive networks in the tumour environment and their therapeutic relevance

Zou, Weiping·2005·Nature Reviews Cancer

DOI 10.1038/nrc1586

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Abstract

It is well known that many tumours are potentially immunogenic, as corroborated by the presence of tumour-specific immune responses in vivo. Nonetheless, spontaneous clearance of established tumours by endogenous immune mechanisms is rare. Therefore, the focus of most cancer immunotherapies is to supplement essential immunogenic elements to boost tumour-specific immunity. Why then has tumour immunotherapy resulted in a generally poor clinical efficiency? The reason might lie in the increasingly documented fact that tumours develop diverse strategies that escape tumour-specific immunity.

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It is likely that the poor response rate across all human cancers is due in part to the multiplicity of molecular mechanisms, many of them regulated by HIFs, by which cancer cells evade the immune system.
“It is likely that the poor response rate across all human cancers is due in part to the multiplicity of molecular mechanisms (90), many of them regulated by HIFs (25), by which cancer cells evade the immune system.”
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In the tumor microenvironment, stimulatory and inhibitory B7 family members are imbalanced, with high inhibitory and low stimulatory expression.
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From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [1]
Tumor-infiltrating immune cells are educated to a tumor-supportive, anti-inflammatory phenotype that significantly promotes tumor neovascularization, metastasis, growth and survival.
“Based on the intimate interplay of tumor cells and tumor-infiltrating immune cells, the latter ones are educated to a tumor-supportive, anti-inflammatory phenotype that significantly promotes tumor neovascularization, metastasis, growth and survival [55].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [55]

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Role for CD4+ CD25+ Regulatory T Cells in Reactivation of Persistent Leishmaniasis and Control of Concomitant Immunity
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Is cancer dangerous to the immune system?
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Gangliosides from Human Melanoma Tumors Impair Dendritic Cell Differentiation from Monocytes and Induce Their Apoptosis
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Enhancing Radiotherapy With Cyclooxygenase-2 Enzyme Inhibitors: A Rational Advance?
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A Novel Fusion Toxin Therapy for Lymphoma
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Principles of cancer therapy: oncogene and non-oncogene addiction
Luo, J., Solimini, N. L., & Elledge, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.02.024 · Cited by 1,765 · see citing works
Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired
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Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells
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The COX-2/PGE2 pathway, key roles in the hallmarks of cancer and adaptation to the tumour microenvironment
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ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis
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B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma
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T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment
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Cytokines and their relationship to the symptoms and outcome of cancer
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Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells
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CD8 + T‐cell memory in tumor immunology and immunotherapy
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Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma
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The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors
Izci, M., Maksoudian, C., Manshian, B. B., & Soenen, S. J. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00779 · Cited by 506 · see citing works
The parallel lives of angiogenesis and immunosuppression: cancer and other tales
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Recent Advances in Cell Membrane–Camouflaged Nanoparticles for Cancer Phototherapy
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Kupffer cell suppression of CD8+ T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions
Wu, K., Kryczek, I., Chen, L., Zou, W., & Welling, T. H. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0901 · Cited by 380 · see citing works
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Tenascin-C induced signaling in cancer
Orend, G., & Chiquet-Ehrismann, R. (2006) · Cancer Letters · doi:10.1016/j.canlet.2006.02.017 · Cited by 384 · see citing works
Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment
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Authors: Zou, W.
Affiliations: Tulane University (US)
Corresponding author: Zou, Weiping
ORCID: Zou, Weiping
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2005-03-18
Volume: 5
Issue: 4
Pages: 263-274
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc1586
OpenAlex: W1984484036
Cited by: 2,057
References: 148
Citations by year: 2026: 43 · 2025: 52 · 2024: 54 · 2023: 104 · 2022: 68 · 2021: 82 · 2020: 100 · 2019: 89 · 2018: 96 · 2017: 101 · 2016: 96 · 2015: 118 · 2014: 113 · 2013: 122 · 2012: 113
FWCI: 11.74
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: tumor immunosuppression, tumor microenvironment, tumor-specific immunity, immune evasion, cancer immunotherapy, tumor immunogenicity
MeSH terms: Antigen-Presenting Cells, Antigens, Neoplasm, Combined Modality Therapy, Dendritic Cells, Humans, Immune Tolerance, Immunotherapy, Membrane Glycoproteins, Neoplasms, Peptides, Antigens, CD, T-Lymphocyte Subsets, B7-1 Antigen, Tumor Escape, B7-H1 Antigen

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