Abstract B94: The role of Th17 cells in the head and neck squamous cell carcinoma evolution.
Authors: Zabrodsky Michal , Betka Jan , Eckschlager Tomas , Rihova Blanka , Boucek Jan 
Published: August 2014

Head and neck squamous cell carcinoma (HNSCC) is the most frequent histotype of the mucosal malignant tumor in this region. Many new diagnostic and therapeutic modalities have been implemented in the diagnostic and treatment protocols however all of them failed to prove a significantly improved overall survival of patient. Surgery combined with radiotherapy and chemotherapy remains a mainstay of the current treatment approaches. A better understanding of the tumor behavior and its immunological profile and microenvironment (e.g. HPV, Treg) allowed us to modify the treatment strategy.

Regulatory T cells (Treg, CD4+CD25+Foxp3+) were described as one of the critical factors for regulation or inhibition of effective anti-cancer immune response. Increased Treg frequency in the peripheral circulation was proven to correlate with the progression HNSCC. In many cancers a synergy of Treg and Th17 (CD4+161+) has been shown. So far, little is known about the importance of Tc17 (CD8+161+) in HNSCC. Particularly, the relationship between Tc17 and tonsillar cancers could be very interesting, because the CCL20 receptor (ligand for CCR6 overexpressed on Tc17) was also frequently found in tonsillar epithelia.

There were 119 patients with HNSCC included in the study from September 2010. Out of 119 primary tumors 50 were localized in the tonsillar region, 42 in the root of the tongue, 20 in the larynx and 7 in hypopharynx. All patients underwent primary surgical therapy, in dependence on the final pathological staging 15 underwent adjuvant chemo-radiation, 73 adjuvant radiation and 31 had no adjuvant therapy.

We examined periphery blood from all patients with the focus on lymphocyte subpopulation (CD3+, CD4+CD25+, CD4+/CD8+, CD19+, CD4+CD45RA+, CD8+CD28-, CD3-CD16+CD56+, CD4+CD25+Foxp3+, CD4+161+, CD8+161+) before the start of anti-tumor therapy. The infiltration of immunocompetent cells in the tumor microenvironment of specimens from primary tumors, from metastases to the neck lymph nodes and from control lymph nodes was measured in a subgroup of patients (68), where samples were taken during the surgery. The correlation of Treg and Th17 resp. Tc17, was analyzed with a special interest.

The percentage of Th17 cells (CD4+CD161+) in peripheral blood does not differ in patients with HNSCC (5.8%, SD 2.5) and in healthy controls (5.6%, SD 3.5, p = 0.46) and also the presence of Tc17 (CD8+CD161+) in peripheral blood shows the same pattern in both groups (7.0%, SD 5.5 vs. 8.0%, SD 4.3, p = 0.31).

The percentage of Th17 cells detected in primary tumors was significantly much higher than in metastatic neck lymph nodes or in neck lymph nodes without metastatic extension (7.1%, SD 7.2 vs. 4.2%, SD 3.0 vs. 4.8%, SD 2.0, p=0.01 resp. p=0.03). There was no difference in the infiltration of Tc17 cells, nor was also observed increased infiltration by Tc17 tonsillar carcinomas compared with other localizations of HNSCC. Very interesting and highly significant was the correlation of Treg infiltration with percentage of Th17 (Treg high vs. Treg low group, CD4+161+: 5.14%, SD 4.63 vs. 8.99%, SD 8.6, p= 0.03) in the samples of primary tumors.

Our results show that Th17 are increasingly detected in the primary HNSCC. Their importance for the prognosis of patients could be analyzed over a longer period of time.

Acknowledgments: The research was supported by IGA MZ CR (Grant No. 11544 and 11542).

Citation Format: Michal Zabrodsky, Jan Betka, Tomas Eckschlager, Blanka Rihova, Jan Boucek. The role of Th17 cells in the head and neck squamous cell carcinoma evolution. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B94.