Abstract B85: The relation between Treg and cancer stem cells in microenvironment of head and neck squamous cell carcinoma.
Authors: Boucek Jan , Zabrodsky Michal , Betka Jan , Eckschlager Tomas , Rihova Blanka 
Published: August 2014

Head and neck squamous cell carcinoma (HNSCC) remains one of the most difficult problems in the current oncology. Overall survival of the patients have not improved in more than 30 years and have not reached approximately 50% at 5 years for all stages. The combination of surgery with radiation or chemotherapy resulted in limited improvement in survival rates, although there was shown the efficacy of concomitant chemo-radiation in organ preservation. On the other hand, identification of some biological or immunological markers (e.g. HPV, Treg) allowed us to better understand the behavior of the disease.

Cancer stem-cell (CSC) theory of tumorigenesis has been established during the last decade. HNSCC is histologically heterogeneous and in tumor microenvironment plays important role also diverses cancer cells, stromal cells and infiltrating inflammatory cells. But only a small subpopulation of CSCs has been identified to be responsible to development and the growth of solid tumors. Several surface epitopes have been published as distinguishing markers for CSCs identification. The most often mentioned are CD44+, CD29+, CD24+ and CD133+ markers.

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 and, consequently, the prognosis and survival for different types of tumors, including HNSCC.

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. Follow-up of all of them has been provided on author´s department.

The presence of the immunocompetent cells in the tumor microenvironment of specimens from primary tumors, from metastases to the neck lymph nodes and from control lymph nodes was correlated with the numbers of HNSCC cancer stem cells (CD44+, CD29+, CD133+) in a subgroup of patients (68), where samples were taken during the surgery.

The number of Treg in specimens from primary tumors was significantly higher than from metastatic neck lymph nodes or in neck lymph nodes without metastatic extension (5.53%, SD 4.12 vs. 3.96%, SD 2.64 vs. 4.9%, SD 3.31, p=0.01). CD44+ or CD29+ or CD133+ cancer stem cells were detected in the tumor microenvironment and the numbers of all of these cells were dramatically higher in samples from primary tumors than from metastases or from control lymph nodes (CD44+: 47.1%, SD 26.4 vs. 28.3%, SD 30.2 vs. 6.5%, SD 16.4, p=0.0002; CD29+: 18.3%, SD 21.7 vs. 12.0%, SD 14.1 vs. 4.4%, SD 12.1, p=0.0028; CD133+: 6.1%, SD 8.7 vs. 3.6%, SD 4.8 vs. 0.6%, SD 0.8, p=0.0002). There was a significant correlation of Treg infiltration with percentage of CD44+ cancer cells (Treg high vs. Treg low group, CD44+ 54.4%, SD 31.3 vs. 40.4%, SD 20.4, p= 0.04) in the samples of primary tumors.

We can conclude that examination of these parameters could be helpful for better understanding of biological behavior of the HNSCC and could help us with prognostication and choice of treatment strategy in HNSCC patients.

Acknowledgments: The research was supported by IGA MZ CR (grant No. 11542).

Citation Format: Jan Boucek, Michal Zabrodsky, Jan Betka, Tomas Eckschlager, Blanka Rihova. The relation between Treg and cancer stem cells in microenvironment of head and neck squamous cell carcinoma. [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 B85.