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STAT3 promotes differentiation of monocytes to MDSCs via CD39/CD73-adenosine signal pathway in oral squamous cell carcinoma

Myeloid-derived suppressor cells (MDSCs) are one of the tumor-infiltrating immune cell population, which play a powerful role in inhibiting anti-tumor immune response. Our previous studies have shown that STAT3 blockade can decrease the number of MDSCs in tumor microenvironment. However, it is unclear for the molecular mechanism of down-regulation MDSCs with STAT3 inhibitor. In this study, we first detected and analyzed the expression of p-STAT3, CD33, CD14, CD39 and CD73 via oral squamous cell carcinoma (OSCC) tissue array. We found that p-STAT3 was positively correlated with CD14, CD33, CD39, and CD73 in OSCC patient specimens. Then we found STAT3 blockade with S3I-201 reduced the expression of CD39/CD73 and the synthesis of adenosine, as well as inhibiting monocytes to MDSCs differentiation in vitro. Furthermore, we found that S3I-201 displayed prominent anti-tumor efficacy in C3H/He OSCC mouse model via inhibiting CD39/CD73-adenosine signal pathway and decreasing MDSCs. These results suggest that STAT3 signal can induce the differentiation of monocytes into MDSCs in tumor microenvironment depending on CD39/CD73-adenosine signal pathway and STAT3 blockade is a promising therapeutic strategy for OSCC.

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This study investigated the mechanism by which the inhibition of STAT3, a signaling molecule, reduces the number of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and enhances anti-tumor immune response in oral squamous cell carcinoma (OSCC) patients. The study found that the expression of p-STAT3 was positively correlated with CD14, CD33, CD39, and CD73 in OSCC tissue, and that blocking STAT3 with the inhibitor S3I-201 reduced the expression of CD39/CD73 and the synthesis of adenosine. The study also found that S3I-201 had anti-tumor efficacy in a mouse model of OSCC, suggesting that inhibiting STAT3 is a promising therapeutic strategy for OSCC.

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Cat.No. Product Name Information
S1155 NSC 74859 (S3I-201) NSC 74859 (S3I-201) shows potent inhibition of STAT3 DNA-binding activity with IC50 of 86 μM in cell-free assays, and low activity towards STAT1 and STAT5.

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