Dynamics of regulatory T cells (Tregs) in patients with oral squamous cell carcinoma

Background and ObjectivesThe immune dysfunction in oral squamous cell carcinoma (OSCC) patients is one of the major factors for growth and dissemination of tumor affecting disease-free survival. MethodsThe phenotypic and functional characteristics of Regulatory T (T-reg) CD4(+)CD25(+)FoxP3(+) subsets in OSCC patients were assessed by multicolor flow cytometry and its effector component (TGF-) by Western blot and qRT-PCR. ResultsAn increased (P<0.05) prevalence of T-reg 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 cell subset, CTLA-4(+), GITR(+), NrP1(+), HLA-DR+, CD127(+), Tbet(+), TGF-(+), and granzyme B+ (GzmB) T-regs also showed a significantly higher prevalence in OSCC patients. Functionally, CD4(+)FoxP3(+) T-regs showed skewed expression of IL-2, IL-10, and IL-35 in patients as compared with the normal controls. Further, enhanced expression of CCR5 and CCR7 on T-regs with up regulation of their ligands (CCL5, CCL19, and CCL21) in tumor cells indicates efficient recruitment and trafficking of T-regs to the tumor site. ConclusionIt seems reasonable to assume that modulation of functional dynamics of selective T-reg subsets may be useful in developing immunotherapeutic strategy for OSCC patients.