Abstract C043: Addition of losartan to FOLFORINOX and chemoradiation downregulates pro-invasion and immunosuppression-associated genes in locally advanced pancreatic cancer

Abstract Purpose: Adding losartan to FOLFIRINOX (FFX) chemotherapy followed by chemoradiation (CRT) resulted in 61% R0 surgical resection our phase II trial patients with locally advanced pancreatic cancer. Here we identify potential mechanisms of benefit assessing the effects neoadjuvant losartan+FFX+CRT versus FFX+CRT on stromal tumor microenvironment. Experimental Design: We performed a gene expression analysis RNA extracted from cancer tissue sections and immunofluorescence for cells immune using archived samples treated (NCT01591733), (NCT01591733) or surgery upfront, without any therapy. then assessed whether certain sets could stratify overall survival patients. Results: Neoadjuvant increased genes linked vascular normalization, transendothelial migration leukocytes, T cell activation cytolytic activity, dendritic related no treatment. In comparison FFX+CRT, downregulated pro-invasion, immunosuppression, M2 macrophages genes, upregulated associated suppression, including p53 pathway. Furthermore, immunostaining revealed significantly less residual disease lesions FFX+CRT. Losartan+FFX+CRT also reduced CD4+FOXP3+ regulatory complete/near complete response. Overall was antigen presentation immunosuppression invasion cell- blood vessel-related those losartan+FFX+CRT. Conclusions: pro-invasion which were improved treatment outcomes Citation Format: Yves Boucher, Jessica M. Posada, Sonu Subudhi, Spencer R. Rosario, Liqun Gu, Ashwin S. Kumar, Heena Kumra, Mari Mino-Kenudson, Nilesh P. Talele, Dan G. Duda, Dai Fukumura, Jennifer Y. Wo, Jeffrey W. Clark, David Ryan, Carlos Fernandez-Del Castillo, Theodore Hong, Mikael J. Pittet, Rakesh K. Jain. Addition FOLFORINOX downregulates immunosuppression-associated [abstract]. In: Proceedings AACR Special Conference Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C043.