Opposing effects of mycotoxins alternariol and deoxynivalenol on the immunomodulatory effects of oxaliplatin and triapine.

Abstract

Mycotoxin occurrence in food worldwide is estimated to increase due to climate change. Moreover, studies on how these food contaminants interfere with medications and especially anticancer therapies are rare. With the rise of anticancer immunotherapies, particularly mycotoxins with immunomodulatory activity, such as alternariol (AOH) or deoxynivalenol (DON), are of great concern. Both mycotoxins interfere with the pro-inflammatory nuclear factor kappa B (NF-κB) pathway in myeloid cells. This pathway not only plays an important role in the anticancer immune response but also inflammatory side effects induced by chemotherapeutic drugs. Consequently, the aim of this study was to investigate possible beneficial or detrimental immunomodulatory interactions between these mycotoxins and anticancer drugs. To assess the combined influence of mycotoxins and anticancer therapies on immune cell stimulation, THP-1 NF-κB reporter cells were utilized as monocytes as well as differentiated and polarized macrophages. Parameters for activation (NF-κB activity and protein expression), differentiation (CD14 and CD71 surface marker expression) and polarization (interleukin 10 (IL10), interleukin 8 (CXCL8), tumor necrosis factor α (TNF), prostaglandin-endoperoxide synthase 2 expression and CXCL8 secretion) were assessed upon combinatory treatment. Both mycotoxins affected the immunostimulatory effects of the pre-selected anticancer drugs oxaliplatin and triapine, although in opposing directions. While AOH generally suppressed a drug-induced activation and increased anti-inflammatory IL10 levels, DON potentiated activation and pro-inflammatory markers, such as CXCL8 and TNF in immune cells. In conclusion, AOH and DON have the potential to alter the immunological effects of anticancer therapies, which should be considered during therapy as well as in their future risk assessment.