Human Th17 cells can be induced through head and neck cancer and have a functional impact on HNSCC development

• Published in: British journal of cancer Vol. 103; no. 8; pp. 1245 - 1254
• Main Authors: Kesselring, R, Thiel, A, Pries, R, Trenkle, T, Wollenberg, B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.10.2010; Nature Publishing Group
• Subjects: 631/250/1619/554/1898/1273; 631/67/327; 692/699/67/1536; Aged; Angiogenesis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - blood supply; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Case-Control Studies; Cell Line, Tumor; Cell Movement - immunology; Cell Proliferation; Cell Transformation, Neoplastic - immunology; Cell Transformation, Neoplastic - pathology; Cytokines; Cytokines - metabolism; Drug Resistance; Epidemiology; Head & neck cancer; Head and Neck Neoplasms - blood; Head and Neck Neoplasms - blood supply; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - pathology; Humans; Inflammation; Leukemic Infiltration - immunology; Lymphatic system; Lymphocyte Activation - immunology; Lymphocyte Activation - physiology; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Medical research; Metastasis; Middle Aged; Molecular Diagnostics; Molecular Medicine; Neovascularization, Pathologic - immunology; Oncology; Otolaryngology; Pathogenesis; Surgery; Th1 Cells - cytology; Th1 Cells - immunology; Th1 Cells - physiology; Tumors; Germany; tumour microenvironment; tumour-infiltrating lymphocytes; Th17; HNSCC; IL-17
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605891

Background: The T helper 17 (Th17) cells recently identified as distinct T helper cell lineage are characterised by their production of the proinflammatory cytokine interleukin 17. Although much effort has been made in understanding the function of Th17 cells in the pathogenesis of different diseases, their influence in carcinogenesis remain largely unknown. Methods: We studied the prevalence and induction of Th17 cells in head and neck squamous cell carcinoma (HNSCC) patients by flow cytometry. To determine the migration mechanism of Th17 cells into primary tumours and metastasis of HNSCC, we performed chemotaxis assays. We analysed the proliferation and the angiogenesis-related proteins of HNSCCs in the presence of Th17 cells with MTT-based proliferation assay and an angiogenesis protein array. Results: In this study, we showed that the prevalence of Th17 cells is elevated in peripheral blood of HNSCC patients. In addition, tumour tissue and tumour-draining lymph nodes are infiltrated by a huge number of Th17 cells representing an important fraction of the tumour-infiltrating lymphocytes (TILs). We further showed that Th17 cells can be induced and expanded in tumour microenvironment through cytokines produced by tumour cells and TILs, and in addition can be recruited to the tumour milieu through a CCR6/CCL20-dependent mechanism. Furthermore, we showed that the proliferation and angiogenesis of HNSCC are impaired in the presence of Th17 cells. Conclusion: We conclude that Th17 cells have a substantial impact on the carcinogenesis of HNSCCs and on their metastasis and could serve as a potential therapeutic target to modulate anti-tumour response in HNSCC.