Impact of Endostatin Gene Therapy on Myeloid-Derived Suppressor Cells From a Metastatic Renal Cell Carcinoma

Abstract

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/3T3LendSN 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 CD11b+Gr-1+ cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11b+Gr-1+ MDSC using the DCFDA marker by flow cytometry. Results: Metastatic RCC (mRCC) induced expansions of CD11b+Gr-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 CD11b+Gr-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.

Function of reactive oxygen species in myeloid-derived suppressor cells

“…Furthermore, endostatin (ES) derived from collagen XVIII has the potential to target PMN-MDSCs selectively, resulting in obviously reduced ROS production ( 122 ). Doxorubicin (Dox), the conventional chemotherapy to reduce the number of MDSCs in tumor tissues and promote antitumor responses, is converted into a liposomal formulation to improve the efficacy of therapy, as well as the peptide named the E75 epitope (Pep) originating from human epidermal growth factor receptor 2 (HER2/neu).…”

Possible Metastatic Stage-Dependent ILC2 Activation Induces Differential Functions of MDSCs through IL-13/IL-13Rα1 Signaling during the Progression of Breast Cancer Lung Metastasis

“…However, these markers are present on multiple immune cells, thus requiring careful exclusion gating for stringent flow cytometric identification of the MDSC subsets. Accordingly, in our study, a certain population of MDSCs was determined by using CD45.2, a hematopoietic marker, following the previously reported panels [46] (Supplementary Figure S5).…”

Association of hypoxia-inducible factor-1α (HIF1α) 1772C/T gene polymorphism with susceptibility to renal cell carcinoma/prostate cancer

“…Renal cell carcinoma is one of the most common renal neoplasms, accounting for approximately 3.9% of new cancers, and its morbidity was also on the rise in the past two decades (Pan et al, 2018;Hu et al, 2017). Cancer prognosis is affected by the underlying tumor biology and also by the host inflammatory response to the disease (Chaves et al, 2018). Surgery and other treatments like conventional chemotherapy and radiotherapy are applied to RCC, but it still has the highest mortality and recurrence rate among the genitourinary carcinomas (Pan et al, 2018;Zhang et al, 2018;Zhao et al, 2018).…”