Abstract
Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) widely participate in the malignant progression in cancer. Previously, we have demonstrated that M1-like TAMs cascaded a stem-like phenotype of oral squamous cell carcinoma (OSCC). Yet, the underlying mechanisms still need to be demonstrated for the regulation of TAMs on cancer stem cells (CSCs) in OSCC. In this study, we investigated a group of CSCs with increased expression of cluster differentiation 10 (CD10), which acted as a mediator in the interaction network between TAMs and tumor-associated neutrophils (TANs) in OSCC. The results showed a significant association between TAMs infiltrations and increased expression of CD10 among all the CSCs-related molecules in OSCC. Then, we validated that OSCC cells with high CD10 expression possessed increased CSCs characteristics. TAMs could drive the heterogenetic CD10(High) CSCs by activating the IL6/STAT3/CD10 pathway. Furthermore, CD10(High) CSCs could recruit and reprogram tumor-associated neutrophils (TANs) in an immunosuppressive state by secreting S100A8/A9 in OSCC. These finding indicated that CD10(High) CSCs played great roles in signaling crosstalk between TAMs and TANs in OSCC, by which infiltrated TAMs drive CD 10(High) CSCs to recruit and reprogram TANs in an immunosuppressive state. Herein, we managed to demonstrate that TAMs could directly regulate a heterogenetic cluster of CSCs with high CD10 expression, and CD10(High) CSCs could recruit and reprogram TANs in OSCC. The novel crosstalk among OSCC-TAMs-CD10(High) CSCs-TANs might bring new prospects for improving the treatment strategies for OSCC patients.