TNFSF12 and Cachexia: These macrophages subsequently secrete CCL5, which activates the NF-κB signaling cascade, leading to the upregulation of TWEAK in tumor cells.289 Elevated TWEAK subsequently initiates muscle remodeling and promotes muscle atrophy via MuRF1 activation.289,290 However, macrophages can also facilitate muscle recovery and regeneration via insulin-like growth factor 1 (IGF-1) autocrine signaling, which shifts polarization toward the M2 phenotype.291 Recent research by Pryce et al. may explain the contrary role of macrophages in cachexia.