Fig. 6.

Interruption of IL-10 signaling improved outcome of chemotherapy. A, H&E staining and metastatic pulmonary tumor nodules counting in subcutaneous Lewis-bearing mice treated with PBS or TANs. The scale bar was 100 μm. B, overall survival of subcutaneous Lewis-bearing mice treated with PBS or TANs. C, tumor volume of subcutaneous Lewis-bearing mice treated with PBS or TANs. D, IL-10 quantification in tumor tissues isolated from subcutaneous Lewis-bearing mice treated with PBS or TANs. E, western blotting of c-Met, p-STAT3 and t-STAT3 in tumor cells isolated from subcutaneous Lewis-bearing mice treated with PBS or TANs. F, schematic diagram of Lewis-bearing mice treatment (treated with TANs, following with IL-10 NAs, chemotherapeutic oxaliplatin or combining treatment). G, tumor volume of Lewis-bearing mice treated with PBS, oxaliplatin, IL-10 NAs or combination. H, metastatic pulmonary tumor nodules counting in subcutaneous Lewis-bearing mice treated with PBS, oxaliplatin, IL-10 NAs or combination. I, overall survival of subcutaneous Lewis-bearing mice treated with PBS, oxaliplatin, IL-10 NAs or combination. J. TANs could promote the malignancy potential of lung cancer cells through paracrine IL-10 signaling, which stimulated the activation of c-Met/STAT3 signaling in tumor cells. In turn, the transcription factor STAT3 increased PD-L1 level in tumor cells, which facilitated neutrophils polarization towards a N2-like status, forming a positive TANs-IL-10-STAT3-PD-L1-TANs feedback loop to stimulate tumor progression. Tumor-derived neutrophils: TANs.