Résumé
Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease, mainly due to patient relapse after chemotherapies. PDAC is characterized by a dense stromal icroenvironment, comprising heterogeneous populations of cancer-associated fibroblasts (CAFs). CAFs play pivotal roles in mediating chemoresistance acquisition. Our research aimsto elucidate the key molecular factors underlying the establishment of distinct CAF sub-identities, which will in turn exert differential effects on the acquisition of tumor chemoresistance.Methods: We established murine patient-derived xenografts (PDX, n¼8 patients), which initially responded to Gemcitabine (Gem) treatment (tumor volume stabilization), but were rendered resistant (tumor volume progression) upon chronic Gem treatment. Multiplex tissue imaging and RNA sequencing (RNA-seq) analyses were conducted on both responsive and resistant tumor specimens. In vitro experiments were performed to elucidate the molecular mechanisms underlying the involvement of a specific CAF factor in chemoresistance acquisition.