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


CONCLUSIONS
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.
Kesselring
R
R
Department for Otorhinolaryngology, University of Luebeck, Ratzeburger Allee 160, Luebeck 23538, Germany.
Thiel
A
A
Pries
R
R
Trenkle
T
T
Wollenberg
B
B
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000097:blood / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D017254:Leukemic Infiltration / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology*
D016207:Cytokines