A Novel Mouse Model to Identify Antigen-Specific Immune Responses in Pancreatic Cancer Cachexia

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Pancreatic Ductal Adenocarcinoma (PDAC) has a poor prognosis and is linked to cancer cachexia, a syndrome of muscle wasting and inflammation.
• The interplay between cachexia and the immune system in PDAC is not well understood, hindering effective treatment strategies.
• A novel preclinical model using the KPCL-4 cell line was developed to study pancreatic cancer cachexia.

Purpose of the Study:

• To characterize a novel pancreatic cancer cachexia model in mice.
• To investigate sex-based differences in cachexia presentation and immune responses within this model.
• To establish a platform for studying cancer cachexia and immunomodulation in PDAC.

Main Methods:

• Orthotopic injection of KPCL-4 cells into male and female C57BL/6J mice.
• Assessment of cachexia hallmarks: tumor weight, body weight, tissue masses, proteolytic markers, and grip strength.
• Analysis of plasma cytokines/chemokines and tumor-infiltrating immune cells using Luminex assay and flow cytometry.

Main Results:

• A sex bias in cachexia was observed, with males showing greater body weight loss and fat loss than females.
• Males exhibited significant skeletal muscle wasting, while females had conserved muscle mass but reduced cross-sectional area and splenomegaly.
• Differential plasma cytokine profiles between sexes suggest immune cell functional differences driving cachexia sex bias.

Conclusions:

• The KPCL-4 orthotopic PDAC model effectively replicates cachexia hallmarks.
• This model demonstrates significant sex-based differences in cachexia presentation and immune profiles.
• The KPCL-4 model provides a valuable platform for exploring cancer cachexia and immunomodulation in PDAC.