Oral squamous cell carcinoma (OSCC) is one of the major cancers affecting Asian countries. The main causative factor has been the 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 (n = 53) with OSCC and healthy individuals (n = 30) by multicoloured flow cytometry. Subsequently we investigated the effects their inhibition via TDG on growth of OSCC cell lines in vitro.
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, CTLA4+, GITR+, NrP1+ and granzyme B + (GzmB) Tregs also showed a significantly higher prevalence in OSCC patients. Functionally CD4+FoxP3+ Tregs showed skewed expression of IL2, IL10 and IL35 in patients as compared with the normal controls. Higher expression of TGFβ in tumor tissues suggests their dominant role in the up regulation of differentiation of Tregs from naive T cells in the tumor bearing host. 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. Treatment with βGBP showed growth promoting effects on Tregs and oral cancer cells. However, the treatment with its inhibitor TDG resulted in inhibition of Treg subsets and also decreased the frequency of IL10+ and IL35+ Tregs indicating its immunomodulatory effects.
Hence, it seems reasonable to assume that 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.
Sadhna Aggarwal
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All authors have declared no conflicts of interest.