Pembrolizumab, Ipilimumab and Nivolumab reduces cardiac pAMPK and IL-10, increases vascular NF-kB expression and levels of IL-1b, IL-2 and IL-6 in myocardial tissue

Abstract Background Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in outcomes. However, several ICIs-induced side effects emerged these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. Purpose We analyzed the differential vasculo and Pembrolizumab, Nivolumab Ipilimumab preclinical models highlighting molecular pathways involved. Methods C57 female mice were treated Ipilimumab, Pembrolizumab (15 mg/kg) through intraperitoneal injection 10 days. pAMPK expression vascular p65/NF-kB was Immunohistochemistry. Cardiac levels IL-1α, IL-1β, IL-2, IL-6 IL-10 quantified ELISA method Results In models, all ICIs increased endothelial cells compared saline group. IHC analysis indicates that reduced myocardial cells. Notably, tissue strongly group vs (p<0.05 saline). On other hand, anti-inflammatory cytokine (overall reduction 43.3–54.5% saline) Conclusion short treatment is sufficient confer pro-inflammatory phenotype heart mice. Furthermore, reductions indicate inhibition mitochondrial metabolism after ICIs. Furthermore induce chemokines involved fibrosis, myocarditis vascultitis. These results could new therapeutic candidates aimed prevent damages patients Funding Acknowledgement Type funding sources: Public Institution(s). Main source(s): Ricerca Corrente, Ministero della Salute