Oral squamous cell carcinoma (OSCC) is one of the major cancers affecting in Asian countries. The main causative factor has been tobacco habit. It has been reported that immune dysfunction in these patients is one of the major factors for tumor growth and dissemination that affects disease-free survival of the patients. We assessed the phenotypic and functional characteristics of Regulatory T (Treg) CD4+CD25+FoxP3+subsets in patients with OSCC by multicoloured flow cytometry. The effects of garcinol mediated, MACS-purified Tregs inhibition on growth of cell lines was also studied. An increased frequency of CD4+CD25+, CD4+FoxP3+, CD8+FoxP3+ and 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+, CTLA-4+, GITR+, NrP1+, HLA-DR+, CD127+, Tbet+ and granzyme B+ (GzmB) Tregs alsoshowed 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. Additionally, garcinol treatment significantly (P < 0.001) inhibited the growth of OSCC cells with a concomitant induction of apoptosis, cell cycle arrest and anti-angiogenesis. It appears that garcinol concurrently prevents many tumour-promoting effects Treg. Hence, modulation of functional dynamics of selective Treg subsets may be useful in enhancing anti tumor immunity and developing immunotherapeutic strategies for patients with oral squamous cell carcinoma.
ALL INDIA INSTITUTE OF MEDICAL SCIENCES,NEW DELHI, INDIA