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IL1RAP is expressed by tumor and stromal cells in pancreatic ductal adenocarcinoma (PDAC). Signaling by IL1 through the IL1R1/IL1RAP complex promotes cancer progression and contributes to the immune suppressive microenvironment in PDAC. The IL1RAP-blocking antibody nadunolimab blocks the signaling of both IL-1a and IL-1b and is currently evaluated in a phase I/IIa clinical study for PDAC (NCT03267316). Cancer-associated fibroblasts (CAFs) are a primary constituent of the PDAC stroma and has previously been shown to be regulated by IL-1. The aim of this study was to explore the functional consequences of nadunolimab treatment on the crosstalk between tumor cells and CAFs. Co-cultures of the PDAC cell line BxPC3 and pancreatic CAFs induced major changes in gene expression of both cell types as determined by RNA sequencing, indicating an extensive communication between the two cell types. Inclusion of nadunolimab to the co-cultures resulted in only 6 differentially expressed genes (padj Citation Format: Nils Hansen, Pablo Peña, Finja Hansen, Petter Skoog, Susanne Larsson Faria, Karin von Wachenfeldt, Carl Högberg, Camilla Rydberg Millrud, David Liberg, Marcus Järås. The IL1RAP-blocking antibody nadunolimab disrupts pancreatic cancer cell and fibroblast crosstalk, reduces recruitment of myeloid cells and inhibits tumor growth [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C055.