Macrophage-derived CCL22 promotes an immunosuppressive tumor microenvironment via IL-8 in malignant pleural effusion
Abstract
Immune dysfunction often occurs in malignant pleural effusion (MPE). In our previous study, TGF-β derived predominantly from macrophages plays an important role in impairing T cell cytotoxicity in MPE. Therefore, we aimed to investigate whether other immunoregulatory cells and factors mediated TGF-β secretion from macrophages, involved in the immunosuppressive microenvironment of MPE, and to provide clues for potential immune therapy for MPE as well. We found that CCL22 level in MPE was significantly higher than that in non-malignant pleural effusion. The high level of CCL22 was closely associated with poor survival in MPE patients with lung cancer. CCL22 was dominantly produced by tumor-associated macrophages (TAMs) in MPE. Meanwhile, TAM-derived TGF-β mediated CCL22 expression in TAMs via c-Fos. CCL22 promoted the recruitment of regulatory T cells (Tregs) in MPE. Lastly, Treg-secreted high level of IL-8 further induced TGF-β production from TAMs, and promoted the immunosuppressive tumor microenvironment in MPE. Our results indicate that macrophage-derived CCL22 plays an important role in the immunosuppressive tumor microenvironment via IL-8 in MPE.
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Many factors in the tumor microenvironment, including cAMP, glucose competition, and oncogenic stress, can induce senescence of T cells, macrophages, natural killer cells, and dendritic cells.
“The role of immunosenescence in tumors is sophisticated: the many factors involved include cAMP, glucose competition, and oncogenic stress in the tumor microenvironment, which can induce the senescence of T cells, macrophages, natural killer cells, and dendritic cells.”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [54]
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- Authors
- Wang, D., Yang, L., Yue, D., Cao, L., Li, L., Wang, D., Ping, Y., Shen, Z., Zheng, Y., Wang, L., & Zhang, Y.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Zhengzhou University (CN)
- Corresponding author
- Zhang, Yi
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 452
- Pages
- 244-253
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2924349996
- Cited by
- 183
- References
- 40
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 35 · 2023: 34 · 2022: 31 · 2021: 27 · 2020: 14 · 2019: 5
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81771781, 81602024, 81872410)
- State's Key Project of Research and Development Plan (2016YFC1303501)
- International Research Cooperation
- Science and Technology Department of Henan Province (162102410059)
- Ministry of Public Health (201501004)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- malignant pleural effusion, CCL22, tumor-associated macrophages, interleukin-8, TGF-beta, regulatory T cells, immunosuppressive tumor microenvironment, lung cancer, c-fos, T cell cytotoxicity, prognostic factors, immunotherapy
- MeSH terms
- THP-1 Cells, Humans, Immune Tolerance, Lung Neoplasms, Macrophages, Pleural Effusion, Malignant, Interleukin-8, Transforming Growth Factor beta, Cell Line, Tumor, T-Lymphocytes, Regulatory, Chemokine CCL22, Tumor Microenvironment
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