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Cited by 215Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesImmune cells in cancer

The DOI matches its Crossref record; 126 of the 126 references it cites were found in a registry or an index.

Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

Open access
Yang, Li, Li, Aitian, Lei, Qingyang, Zhang, Yi·2019·Journal of Hematology & Oncology
DOI 10.1186/s13045-019-0804-8PMC PMC6880373
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Abstract

Immunotherapy is a currently popular treatment strategy for cancer patients. Although recent developments in cancer immunotherapy have had significant clinical impact, only a subset of patients exhibits clinical response. Therefore, understanding the molecular mechanisms of immunotherapy resistance is necessary. The mechanisms of immune escape appear to consist of two distinct tumor characteristics: a decrease in effective immunocyte infiltration and function and the accumulation of immunosuppressive cells in the tumor microenvironment. Several host-derived factors may also contribute to immune escape. Moreover, inter-patient heterogeneity predominantly results from differences in somatic mutations between cancers, which has led to the hypothesis that differential activation of specific tumor-intrinsic pathways may explain the phenomenon of immune exclusion in a subset of cancers. Increasing evidence has also shown that tumor-intrinsic signaling plays a key role in regulating the immunosuppressive tumor microenvironment and tumor immune escape. Therefore, understanding the mechanisms underlying immune avoidance mediated by tumor-intrinsic signaling may help identify new therapeutic targets for expanding the efficacy of cancer immunotherapies.

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Fig. 1 Tumor-intrinsic signaling induces the exclusion and dysfunction of effective immunocytes. Oncogenic drivers of tumors, including β-catenin, STAT3, PI3K/PTEN/AKT/mTOR, p53, NF-κB, and RAS/RAF/MAPK signaling, are activated in the tumor microenvironment. These oncogenic signaling pathways not only downregulate the production of chemokines, which further decrease the recruitment of DCs, macrophages, T cells, and NK cells to tumor sites, but also induce immunosuppression of these immunocytes. In addition, tumor-intrinsic signaling can induce PD-L1 expression in tumor cells, leading to T cell dysfunction in the tumor microenvironment
Fig. 1 Tumor-intrinsic signaling induces the exclusion and dysfunction of effective immunocytes. Oncogenic drivers of tumors, including β-catenin, STAT3, PI3K/PTEN/AKT/mTOR, p53, NF-κB, and RAS/RAF/MAPK signaling, are activated in the tumor microenvironment. These oncogenic signaling pathways not only downregulate the production of chemokines, which further decrease the recruitment of DCs, macrophages, T cells, and NK cells to tumor sites, but also induce immunosuppression of these immunocytes. In addition, tumor-intrinsic signaling can induce PD-L1 expression in tumor cells, leading to T cell dysfunction in the tumor microenvironmentCC BY · PubMed Central
Fig. 2 Tumor-intrinsic signaling mediates the recruitment and differentiation of immunosuppressive cells. Oncogenic pathways in tumor cells can be activated to promote the production of several chemokines and cytokines, which further enhance the recruitment and polarization of immunosuppressive cells, such as TAMs, MDSCs, Tregs, and TANs, to tumor sites. These immunosuppressive cells within the tumor microenvironment may also contribute to immunoresistance in cancers
Fig. 2 Tumor-intrinsic signaling mediates the recruitment and differentiation of immunosuppressive cells. Oncogenic pathways in tumor cells can be activated to promote the production of several chemokines and cytokines, which further enhance the recruitment and polarization of immunosuppressive cells, such as TAMs, MDSCs, Tregs, and TANs, to tumor sites. These immunosuppressive cells within the tumor microenvironment may also contribute to immunoresistance in cancersCC BY · PubMed Central
Fig. 3 Tumor-intrinsic signaling as a therapeutic target for cancers. The activation of tumor-intrinsic signaling regulates and promotes the immunosuppressive tumor microenvironment, which includes exclusion and dysfunction of effective immunocytes and recruitment and differentiation of immunosuppressive cells. Therefore, targeting the tumor-intrinsic signaling is a potential strategy for cancer treatment
Fig. 3 Tumor-intrinsic signaling as a therapeutic target for cancers. The activation of tumor-intrinsic signaling regulates and promotes the immunosuppressive tumor microenvironment, which includes exclusion and dysfunction of effective immunocytes and recruitment and differentiation of immunosuppressive cells. Therefore, targeting the tumor-intrinsic signaling is a potential strategy for cancer treatmentCC BY · PubMed Central

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Metadata

Authors
Yang, L., Li, A., Lei, Q., & Zhang, Y.
Affiliations
  • First Affiliated Hospital of Zhengzhou University (CN)
  • Zhengzhou University (CN)
Corresponding author
Zhang, Yi
ORCID
Venue
Journal of Hematology & Oncology
Publisher
Springer Science and Business Media LLC
Published
2019-11-27
Volume
12
Issue
1
Pages
125-125
ISSN
1756-8722 (ISSN-L)
DOI
10.1186/s13045-019-0804-8
PMC
PMC6880373
OpenAlex
W2990431514
Cited by
215
References
126
Citations by year
2026: 27 · 2025: 40 · 2024: 29 · 2023: 31 · 2022: 39 · 2021: 28 · 2020: 20
FWCI
2.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Hematology & Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (U1804281, 81771781, 81602024)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
immunosuppressive tumor microenvironment, tumor immune evasion, cancer immunotherapy resistance, immune exclusion, interpatient heterogeneity, somatic mutations, immune cell infiltration, therapeutic target
MeSH terms
Antineoplastic Agents, Humans, Immunosuppressive Agents, Immunotherapy, Neoplasms, Signal Transduction, Tumor Escape, Molecular Targeted Therapy, Tumor Microenvironment

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