IL-10 is one of the major cytokines, which is significantly involved in immunosuppressive and pro-tumoural processes in the immune system. IL-10 is mainly produced by tumor associated macrophages, T regulatory cells (Tregs) and T helper (Th) 2 cells but also by bronchial epithelial cells, which are the initial cellular source of Non-Small Cell Lung Cancer. Moreover, IL-10 is able to inhibit Th1 cells, antigen presenting cells and classical-activated macrophages, which play an important role in tumor defense.
In a previous human study of our working group, we found an elevated number of IL-10 positive cells in the lung tumors, of patients who suffered from ADC compared to their tumor free lung control region. In our murine model of ADC, we analysed IL-10 knockout mice. Here we detected significantly less tumor development compared to their controls. Cell based analysis showed an increased amount of Tbet+ B-cells and higher Immunoglobulin G serum levels in IL-10KO mice compared to their controls. In line with these findings, we found an elevated amount of Th1 cells, which are important players for tumor defense. IL-10KO mice showed an increased number of Tbet+ CD8+ cytotoxic T cells and a significantly enhanced levels of tumor necrosis factor α. Moreover, tumor bearing IL-10KO mice showed decreased amount of tumor infiltrating macrophages.
In conclusion, the loss of IL-10 leads to an improved anti-tumoural immune response in the microenvironment and thus might be an important target for immunotherapy.