Tumor microenvironments direct the recruitment and expansion of human Th17 cells
Abstract
Although Th17 cells play critical roles in the pathogenesis of many inflammatory and autoimmune diseases, their prevalence among tumor-infiltrating lymphocytes (TILs) and function in human tumor immunity remains largely unknown. We have recently demonstrated high percentages of Th17 cells in TILs from ovarian cancer patients, but the mechanisms of accumulation of these Th17 cells in the tumor microenvironment are still unclear. In this study, we further showed elevated Th17 cell populations in the TILs obtained from melanoma and breast and colon cancers, suggesting that development of tumor-infiltrating CD4(+) Th17 cells may be a general feature in cancer patients. We then demonstrated that tumor microenvironmental RANTES and MCP-1 secreted by tumor cells and tumor-derived fibroblasts mediate the recruitment of Th17 cells. In addition to their recruitment, we found that tumor cells and tumor-derived fibroblasts produce a proinflammatory cytokine milieu as well as provide cell-cell contact engagement that facilitates the generation and expansion of Th17 cells. We also showed that inflammatory TLR and nucleotide oligomerization binding domain 2 signaling promote the attraction and generation of Th17 cells induced by tumor cells and tumor-derived fibroblasts. These results identify Th17 cells as an important component of human TILs, demonstrate mechanisms involved in the recruitment and regulation of Th17 cells in tumor microenvironments, and provide new insights relevant for th…
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RANTES and MCP-1 secreted by tumor cells and tumor-derived fibroblasts mediate the recruitment of Th17 cells.
“RANTES and MCP-1 secreted by tumor cells and tumor-derived fibroblasts mediate the recruitment of Th17 cells (159).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [159]
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- Authors
- Su, X., Ye, J., Hsueh, E. C., Zhang, Y., Hoft, D. F., & Peng, G.
- Affiliations
- Division of Immunobiology, Department of Internal Medicine
- Saint Louis University (US)
- Corresponding author
- Su, Xinming
- Ye, Jian
- Peng, Guangyong
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12-21
- Volume
- 184
- Issue
- 3
- Pages
- 1630-1641
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2138402519
- Cited by
- 324
- References
- 10
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 12 · 2023: 17 · 2022: 19 · 2021: 17 · 2020: 26 · 2019: 14 · 2018: 12 · 2017: 23 · 2016: 16 · 2015: 20 · 2014: 21 · 2013: 35 · 2012: 36
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R21AI097852)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- Th17 cells, tumor microenvironment, tumor-infiltrating lymphocytes, RANTES, MCP-1, Toll-like receptor signaling, cell-cell contact, ovarian cancer, melanoma, breast cancer, colon cancer, cancer immunotherapy
- MeSH terms
- Breast Neoplasms, Cell Communication, Cell Differentiation, Cell Movement, Cell Transformation, Neoplastic, Colonic Neoplasms, Female, Fibroblasts, Humans, Melanoma, CD4-Positive T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Coculture Techniques, Cancer Vaccines, Interleukin-17, Cell Line, Tumor
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