ROS production by circulating phagocytes and Guerin carcinoma resistance to cisplatin

Abstract

Background: Tumor drug resistance remains a primary cause of unsuccessful cancer therapy. The search for biological markers of the sensitivity/resistance of malignant neoplasms to drug therapy is an urgent and important task, the solution of which will increase the effectiveness of anticancer chemotherapy. Aim: To study the relationship between the functional activity (parameters of the phagocytosis and reactive oxygen species (ROS) production) of neutrophils and monocytes in the peripheral blood of rats with transplanted Guerin carcinoma and the degree of its sensitivity to cisplatin (Cpt). Materials and Methods: The original and Cpt-resistant variants of Guerin carcinoma were transplanted to female Wistar rats 2.5 months old. The parameters of the phagocytic activity of circulating neutrophils and monocytes were determined by the degree of ingestion of inactivated and FITC-labeled staphylococci using flow cytometry. The number of ROS-generating cells and the intensity of ROS production by phagocytes were determined by flow cytometry using 2’,7’-dichlorodihydrofluorescein diacetate. Results: The growth of both variants of Guerin carcinoma caused a statistically significant decrease in the intensity of neutrophil phagocytosis by more than 47% with a tendency to the reduction of the intensity of phagocytosis by monocytes. The phagocytic activity of circulating neutrophils and monocytes did not differ significantly between the groups of animals with the original and Cpt-resistant variant of Guerin carcinoma. In contrast, the intensity of ROS generation by both monocytes and neutrophils in the peripheral blood of animals with Cpt-resistant tumor increased by more than 86% as compared to original carcinoma-bearing rats. Conclusion: This study provides evidence that the intensity of ROS production by circulating monocytes and neutrophils may reflect the degree of tumor sensitivity to Cpt. Increased intensity of ROS production could serve as a pretreatment predictor of the formation of tumor drug resistance.

Flow Cytometry of Oxygen and Oxygen-Related Cellular Stress

“…•− , hypochlorous acid or NO [107]. With these limitations, H 2 DCF has been successfully applied to studies of oxidative burst in phagocytes [110,111] and to assess oxidative processes in different cell models [112][113][114][115][116].…”

Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors

“…The role of neutrophil ROS production and its effects on tumor cell growth or death are likely to depend on the particular neutrophil phenotype predominating within the tumor microenvironment and the local ROS levels that they release. Thus, several studies have implicated neutrophil-mediated ROS production in promoting tumor colonization [ 29 ] and chemotherapy resistance [ 30 ]. However, it is clear that by using appropriate factors it is possible to enhance and promote beneficial neutrophil recruitment and activation such as IL-17 [ 31 ], bacterial-based products [ 32 , 33 ] or poly I:C double-stranded RNA [ 34 ], and these neutrophils provide potent anti-tumor immunity involving greater ROS production as detailed in the following sections.…”