Given its various roles in PDAC, lipolysis, and muscle wasting, here we investigated the effects of IL-6 emanating from PDAC tumor cells on tissue crosstalk and cachexia using patient-derived orthotopic xenografts and mouse PDAC cells deleted for IL-6 (KPC IL6KO) in a mouse model of pancreatic cancer cachexia. Here, IL6 is linked to neoplasm.