The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia

With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages in potentiating pancreatic cancer induced muscle wasting via promoting TWEAK (TNF-like weak inducer of apoptosis) secretion from the tumor. Specifically, depletion of macrophages reverses muscle degradation induced by tumor cells. Macrophages induce non-autonomous secretion of TWEAK through CCL5/TRAF6/NF-κB pathway. TWEAK promotes muscle atrophy by activating MuRF1 initiated muscle remodeling. Notably, tumor cells…

• VC
  Virginia Commonwealth University
• WA
  William and Ella Owens Medical Research Foundation

  Award: R01 CA203108
• NI
  National Institutes of Health

  Awards: R01 CA247234, R01 CA203108, CA225520, R01 CA186338, P30 CA225520
• NC
  National Cancer Institute

  Awards: P30 CA225520, R01 CA247234, CA203108, R01 CA203108, R01 CA186338