1241 IL-1 blockade prevents cardiac toxicity and improves immunotherapy efficacy in mouse models of pancreatic cancer

• DOI: 10.1136/jitc-2022-sitc2022.1241
• Publication Date: 2022-11-08T01:21:30Z
• Authors: Rakesh Jain; Nilesh Talele; Heena Kumra; Igor Gomes Dos Sa...; Sylvie Roberge; William Ho; Patrik Andersson; Sampurna Chatterjee; Marie Siwicki; Dan Duda; Mikael Pittet; Dai Fukumura; Rakesh Jain
• Keywords: FOLFIRINOX; Cardiotoxicity

<h3>Background</h3> Immune checkpoint blockers (ICBs) have revolutionized cancer treatment, but they are often associated with severe immune related adverse events (irAEs). These irAEs more seen in patients obesity or concomitantly treated cytotoxic therapies. <h3>Methods</h3> We aimed to understand the mechanisms of ICB-induced irAEs, context [FD1] and ICB/chemotherapy combinations. used a mouse model cardiac which is most fatal type irAE ICB-treated patients, clinically relevant features: (i) an ICB-resistant (pancreatic ductal adenocarcinoma PDAC), (ii) induced high-fat diets, (iii) combination treatment ICB (α-PD1 + α-CTLA4) chemotherapy (FOLFIRINOX[FD2] <h3>Results</h3> Mice orthotopic PDAC developed after as compared chow diet. recapitulated those observed obesity, including dysfunction consistent myocarditis, fibrosis, increased circulating levels interleukin-1 beta (IL-1b). IL-1b blockade prevented myocarditis reduced fibrosis immunotherapy. Importantly, also enhanced anti-tumor effects FOLFIRINOX therapy, survival. <h3>Conclusions</h3> Using translationally model, we discovered that mediates cardiotoxicity, patients. In addition, found blockers, already clinic for other indications[FD1] , may both reduce enhance antitumor triggered by