Endostatin gene therapy inhibits intratumoral macrophage M2 polarization.

摘要: Abstract Background Renal cell carcinoma (RCC) is a highly vascularized cancer resistant to chemotherapy and radiotherapy. RCC frequently infiltrated with immune cells, macrophages being the most abundant type. Alternatively activated M2 are known contribute tumor progression. Endostatin (ES) fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we investigated impact ES gene therapy on polarization tumor-associated (TAMs) in lung metastases from tumor-bearing mice. Methods BALB/c mice divided into three groups: Normal, Control ES-treated. Tumor-bearing were treated ES-transduced cells or control over ten days. At end plasma was collected, pulmonary isolated used for FACS RT-PCR. ELISA tests analyze culture supernatant cytokines. Results treatment significantly reduced levels anti-inflammatory pro-angiogenic cytokines, including IL4, IL-10, IL-13 VEGF. Gene expression markers, such as Arg-1, VEGF YM-1, declined significantly. Flow cytometry showed reduction number F4/80 + CD36 + CD206 + CD209+ IL-10 secretion by these cells. Reduced also found supernatants ES-treated group. Conclusions Our research corroborates previous observations has an important anti-tumoral role. However, aside promoting interferon-ɤ effective T response, show here switch extended TAMs, complicating maintenance pro-tumorigenic thus favoring elimination.