Interleukin-7 enhances recruitment of MDSCs by regulating MCP-1 via JAK1/STAT3 signaling pathway in non-small cell lung cancer

Lung Cancer is one of the most commonly diagnosed cancers worldwide and the leading cause of cancer-related deaths worldwide. In recent years, an increasing number of studies have shown that the tumor immune microenvironment (TIME) has a significant impact on the development of lung Cancer. Interleukin-7 (IL-7) is an essential cytokine for the adaptive immune system and plays an important immunoregulatory role in different types of tumors. However, the relationship between IL-7 and TIME in non-small cell lung Cancer (NSCLC) is not yet known. This study found that the expression of MCP-1 and CD11b was correlated with the expression of IL-7/IL-7R. MCP-1, IL-7R, tumor differentiation and tumor stage were the strongest predictors of survival. In addition, IL-7 upregulates MCP-1 through JAK1/STAT3 pathway to affect the migration of MDSCs and exert tumor immunosuppressive effect. Furthermore, CCR2 Inhibitor and depletion of MDSCs suppressed the promoting effect of IL-7 mediated development of lung Cancer. These findings provided the important mechanism that IL-7 upregulate MCP-1 through JAK1/STAT3 pathway to recruit MDSCs and put forth blockage of CCR2 Inhibitor and MDSCs recruitment as a prospective immunotherapy strategy for the treatment of NSCLC.

IL-7; MCP-1; MDSCs; NSCLC.