Objective: Macrophages and myeloid-derived suppressor cells (MDSCs) are key immune cells within the tumor microenvironment. Activation of the stimulator of interferon genes (STING) pathway and its downstream secretion of C-X-C motif chemokine ligand 10 (CXCL10) can suppress tumor development. This study investigated whether the STING–CXCL10 axis inhibits tumor progression by preventing macrophage M2 polarization and the differentiation of bone marrow cells (BMCs) into MDSCs.

Methods: Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to assess the expression levels of STING and CXCL10. Lung cancer cell culture supernatants were collected and co-cultured with macrophages and bone marrow cells (BMCs). Flow cytometry was employed to evaluate macrophage polarization and the differentiation of MDSCs. Enzyme-linked immunosorbent assay (ELISA) was performed to measure CXCL10 levels in the lung cancer cell culture supernatant. To assess cell viability and invasion, BMCs or M0 macrophages were co-cultured with lung cancer cells, and the roles of STING and CXCL10 in these processes were analyzed.

Results: STING signal pathway is downregulated in lung cancer cell lines. Silencing of STING promotes macrophage M2 polarization and BMCs to MDSCs differentiation. In addition, knockdown of STING led to a downregulation of CXCL10 levels. Effects of STING overexpression were abolished by neutralizing antibody to CXCL10 (NAb-CXCL10). Co-culture of lung cancer cells with M0 macrophages or BMCs enhanced their viability and invasive capacity, whereas STING overexpression inhibited these effects by upregulating CXCL10.

Conclusions: This study suggests that the activation of the STING/CXCL10 axis inhibits macrophage M2 polarization and differentiation of BMCs to MDSCs. This study further suggests that the STING/CXCL10 axis is a potential target for lung cancer therapy.