Abstract A67: Phenotypic and functional dynamics of CD4+CD25+FOXP3+ regulatory T cells in patients with tobacco-related oral squamous cell carcinoma

Abstract

Abstract Background: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers worldwide. Dysregulation of immune response plays a major role in establishment and development of cancer. CD4+CD25+FoxP3+ regulatory T cells (Tregs) have been reported to downregulate effector immune functions and its inactivation have been associated with development of autoimmune diseases. We therefore investigated the phenotypic and functional dynamics of CD4+CD25+FoxP3+ (Tregs) cells in tobacco-related OSCC patients. Aim: Aim of the study was to investigate the phenotypic and functional characteristics of Tregs cells in OSCC patients in terms of their subsets, expression of functional markers and cytokine profile etc. Methods: The phenotypic and functional characteristics of Treg subsets in patients with OSCC were assessed by multicolour flowcytometry. The levels of TGFβ were assessed by realtime PCR and western blot. Results: An increased (p<0.05) prevalence of Tregs phenotypes (CD4+CD25+, CD4+FoxP3+, CD8+FoxP3+, CD4+CD25+FoxP3+) was observed in the peripheral circulation of OSCC patients that positively correlated with clinicopathological features. The increased frequency of CD4+CD8+CD25+FoxP3+, a unique T cells subset also showed significantly higher prevalence in OSCC patients. Functionally CD4+FoxP3+ Tregs showed skewed expression of IL-2, IL-10 and IL-35 in patients as compared with the normal controls. Higher expression of TGF-β in tumour tissues suggests their dominant role in upregulation of differentiation of Tregs from naive T cells in tumour bearing host. Further enhanced expression of CCR5 and CCR7 on Tregs with upregulation of their ligands (CCL5, CCL19 and CCL21) in tumour cells indicate efficient recruitment and trafficking of Tregs to the tumour site. Conclusions: Accumulation of heterogeneous subsets of Tregs in the peripheral circulation indicates their suggestive role in immuno-suppression leading to growth and proliferation of OSCC. Therefore manipulation of Tregs can be added to the therapeutic armamentarium for enhancing anti-tumour immunity in OSCC patients. Note: This abstract was not presented at the conference. Citation Format: Satya N. Das, Sadhna Aggarwal, Suresh C. Sharma. Phenotypic and functional dynamics of CD4+CD25+FOXP3+ regulatory T cells in patients with tobacco-related oral squamous cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A67.