通过转化生长因子-β抑制剂改善口腔鳞状细胞癌中细胞毒性 T 淋巴细胞的功能

Immunotherapy with immune-checkpoint therapy has recently been used to treat oral squamous cell carcinomas (OSCCs).

However, improvements in current immunotherapy are expected because response rates are limited. Transforming growth factor-β (TGF-β) creates an immunosuppressive tumor microenvironment (TME) by inducing the production of regulatory T-cells (Tregs) and cancer-associated fibroblasts and inhibiting the function of cytotoxic T-lymphocytes (CTLs) and natural killer cells.

TGF-β may be an important target in the development of novel cancer immunotherapies. In this study, we investigated the suppressive effect of TGF-β on CTL function in vitro using OSCC cell lines and their specific CTLs.

Moreover, TGFB1 mRNA expression and T-cell infiltration in 25 OSCC tissues were examined by in situ hybridization and multifluorescence immunohistochemistry.

We found that TGF-β suppressed the function of antigen-specific CTLs in the priming and effector phases in vitro.

Additionally, TGF-β inhibitor effectively restored the CTL function, and TGFB1 mRNA was primarily expressed in the tumor invasive front. Interestingly, we found a significant negative correlation between TGFB1 mRNA expression and the CD8 + T-cell/Treg ratio and between TGFB1 mRNA expression and the Ki-67 expression in CD8 + T-cells, indicating that TGF-β also suppressed the function of CTLs in situ.

Our findings suggest that the regulation of TGF-β function restores the immunosuppressive TME to active status and is important for developing new immunotherapeutic strategies, such as a combination of immune-checkpoint inhibitors and TGF-β inhibitors, for OSCCs.