Interaction between CAFs and apoptotic cancer cells promotes OSCC proliferation via STING signaling

Apoptosis can fuel oncogenesis by the education of surrounding stromal cells. However, the function of cancer-associated fibroblasts (CAFs), which interacted with apoptotic cancer cells, in oral squamous cell carcinoma (OSCC) progression is still unknown. This study aimed to explore the prognostic value of apoptosis and the biological effects of CAFs, interacted with apoptotic cancer cells, on OSCC. A total of 166 samples from OSCC patients were stained via TUNEL reaction to evaluate the correlation between apoptosis and clinical characteristics. Cell viability and proliferation were assessed through flow cytometry and CCK-8 assays, respectively. Levels of mRNA and protein were examined through qRT-PCR, western blot and immunofluorescence. Higher percentage of apoptotic cancer cells in OSCC positively correlated with more Ki67 cells and predicted poor clinical outcomes. Conditioned medium from CAFs exposed to apoptotic cancer cells significantly facilitated cell proliferation. Co-culture CAFs with apoptotic cancer cells dampened the phosphorylation of STING/IRF3 signaling, as well as the production of type I interferon, which was required for the inhibition of OSCC cell proliferation. These results demonstrate the interplay between apoptotic cancer cells and CAFs promotes OSCC proliferation via STING signaling, identifying a potential therapy targeted CAFs surrounded with apoptotic cancer cells for OSCC.