Defining the adipose immune environment in PDAC associated cachexia and pre-cachexia

• Applicant: Dr. Max Heckler
• Subject Area: General and Visceral Surgery
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569718828

Cachexia with adipose tissue wasting is common in pancreatic cancer patients and limits prognosis and quality of life. The immune system plays a key role in the maintenance of adipose tissue in health and disease, but data on the immune environment of wasting adipose tissue is limited. In preliminary experiments, we found that eosinophils and alternatively activated macrophages (AAMs) are abundant in adipose tissue of cancer-bearing cachectic mice and humans, and that AAMs induce adipocytic lipolysis in co-culture models. Macrophage derived Apolipoprotein E (ApoE) was upregulated in murine and human pancreatic cancer cachexia and correlated with lipolysis. We hence hypothesize that cells from the immune environment of adipose tissue, specifically macrophage subpopulations, influence and maintain the catabolic state that characterizes cachexia. Our specific aims will test the following hypotheses: I) Adipose tissue of cachectic and pre-cachectic pancreatic cancer patients exhibits an aberrant immune environment. This immune phenotype correlates with disease severity and postoperative outcome. II) AAM-adipocyte crosstalk affects adipose tissue wasting in human pancreatic cancer patients and murine models of pancreatic cancer. Adipose tissue wasting is affected by modulation of this immunometabolic junction.

• DFG Programme: Research Grants