Abstract 2183: Immunomodulation by oxaliplatin is affected by the mycotoxin food contaminants alternariol and deoxynivalenol in opposite directions

Abstract

Abstract Our diet does not only impact our risk for cancer, but might also affect the outcome of anti-cancer therapies. While interaction of natural food constituents or supplements with anticancer therapies are frequently investigated, studies on how food contaminants, such as mycotoxins, interfere with anticancer drugs is rare or lacking, despite the rise of mycotoxin occurrence in food worldwide. As the importance of the immune system during anticancer therapies is now well known, especially mycotoxins with immunomodulatory activity, such as alternariol (AOH) or deoxynivalenol (DON), which were reported as immunosuppressive and immunostimulatory, respectively, are of great concern. Thus, the aim of this study was to investigate possible disadvantageous or beneficial interactions of the mycotoxins AOH or DON with the clinically routinely-used oxaliplatin, a known stimulator of the anticancer immune response as well as immunogenic cell death inducer. Effects of the mycotoxin-oxaliplatin combinations on cell viability of different colon carcinoma cell models were analyzed via CellTiter Blue, showing a mostly additive increase of anticancer activity with both mycotoxins. As the immune system was reported to play an important role in the anticancer activity of oxaliplatin, the combined influence of mycotoxins and anticancer therapies on immune cell stimulation was analyzed. To that end, monocytic THP-1 Lucia NF-κB reporter cells were utilized and their activation, differentiation and polarization was monitored during combinatorial treatment, via luminescence, flow cytometry and qPCR, respectively. In line with its more immunostimulatory activities, oxaliplatin alone activated NF-κB signaling in monocytic THP-1 cells. However, this increase in signaling was significantly suppressed in combination with AOH, while DON further enhanced the activation significantly. In line, during polarization of THP-1 macrophages to pro- (M1) or anti-inflammatory (M2) mediators, oxaliplatin strongly induced M1 markers (IL-8, TNF-α and COX-2) on mRNA level, not altering the NF-κB activity but partly downregulating M2 marker IL-10. This M1 stimulation was potentiated in the combination with DON, whereas AOH stimulated M2 marker expression. In conclusion, AOH was able to suppress the immunostimulatory potential of oxaliplatin, whereas DON enhanced it. Consequently, mycotoxins might affect the outcome of especially immunologically-active therapies. This should not only be considered in future risk assessment of food contaminants, but might also be a chance to fine-tune the anticancer immune response. Citation Format: Sonja Hager, Judith Gufler, Walter Berger, Petra Heffeter, Doris Marko. Immunomodulation by oxaliplatin is affected by the mycotoxin food contaminants alternariol and deoxynivalenol in opposite directions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2183.