Impact of endostatin gene therapy on myeloid-derived suppressor cells from a metastatic renal cell carcinoma.

AIM

To evaluate the role of endostatin (ES) gene therapy on myeloid-derived suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC).

MATERIALS AND METHODS

Balb/C mice bearing orthotopic Renca tumors were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in vivo experiment, plasma and tissue lung samples were collected. Plasma ES and granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and Milliplex, respectively. Quantification of CD11bGr-1 cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11bGr-1 MDSC using the DCFDA marker by flow cytometry.

RESULTS

Metastatic RCC (mRCC) induced expansions of CD11bGr-1 MDSC and promoted accumulation of these cells and their subtypes in lymphoid organ and metastases. ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor microenvironment, reflecting the reduced metastatic accumulation of CD11bGr-1 MDSC in the lungs. However, the therapy was selective for granulocytic cells, thus reducing the production of ROS.

CONCLUSION

These findings confirm the expansion of MDSC during metastatic progression of RCC and indicate the important role of ES in reducing MDSC and possible use of ES therapy in combined anticancer treatment.