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

BACKGROUND AND OBJECTIVES: The 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.

METHODS: The phenotypic and functional characteristics of Regulatory T (Treg ) CD4+ CD25+ FoxP3+ subsets in OSCC patients were assessed by multicolor flow cytometry and its effector component (TGF-β) by Western blot and qRT-PCR.

RESULTS: An increased (P < 0.05) prevalence of Treg 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-β+ , and granzyme B+ (GzmB) Tregs also showed a 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. Further, enhanced expression of CCR5 and CCR7 on Tregs with up regulation of their ligands (CCL5, CCL19, and CCL21) in tumor cells indicates efficient recruitment and trafficking of Tregs to the tumor site.

CONCLUSION: It seems reasonable to assume that modulation of functional dynamics of selective Treg subsets may be useful in developing immunotherapeutic strategy for OSCC patients.