Abstract A068: Imbalance in regulatory T (Treg) cells frequency in peripheral circulation of patients with oral squamous cell carcinoma and their effects on growth of oral cancer

Abstract

Abstract Regulatory T (Treg) cells play a major role in establishment and maintenance of self tolerance of immune system. Deficit in the numbers of Tregs contributes to the development of autoimmune diseases, allergy and graft rejection whereas abundance of Tregs suppresses anti-tumour immune response leading to tumour immuno-evasion. In this study, we have estimated the frequency of distinct immune cells, Tregs and its phenotypic subsets in patients with Oral Squamous Cell Carcinoma (OSCC) by multicolour flowcytometry. Subsequently we investigated the effects of MACS sorted Tregs on growth/proliferation/angiogenesis of OSCC cell lines in vitro. Frequency of all the effector type anti-tumour immune cells such as CD8+ T-cells, NK (CD56+) and NKT (CD3+CD56+) cells was found to be decreased whereas CD3+, CD4+, γδ-T cells were upregulated in OSCC patients. We observed significantly increased (p < 0.05) prevalence of Tregs and their phenotypic subsets (CD4+CD25+, CD4+FoxP3+, CD8+FoxP3+, CD4+CD25+FoxP3+) in peripheral circulation of OSCC patients as compared to that of the normal individuals. Our study further showed a definite association between the OSCC progression and elevated Tregs frequency. An association between reciprocally regulated Treg and Th17 cells was also observed. The increased frequency of CD4+CD8+CD25+FoxP3+, a unique T cells subset was seen in OSCC patients. The CTLA-4+ and GITR+ Tregs also showed higher occurrence in patients indicating their contribution to the immuno-suppressive function of Tregs in OSCC. Introduction of MACS isolated Treg cells to in vitro oral cancer cell culture resulted in increased proliferation and expression of angiogenic marker VEGF by cancer cells showing that these suppressor cells helps in growth and proliferation of OSCC cells. Accumulation of heterogeneous subsets of Tregs in the peripheral circulation indicates their suggestive role in tumour induced immuno-suppression as well as in growth and proliferation of oral cancer cells. Therefore, inhibitory manipulation of Tregs, in terms of their frequency and functional activity, can be added to the therapeutic armamentarium for enhancing anti-tumour immunity in OSCC patients and preventing the establishment and progression of oral cancer. Citation Format: Sadhna Aggarwal, Satya N. Das, Suresh C. Sharma. Imbalance in regulatory T (Treg) cells frequency in peripheral circulation of patients with oral squamous cell carcinoma and their effects on growth of oral cancer. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A068.