Multiple Cancer Cell Types Release LIF and Gal3 to Hijack Neural Signals (add PyMT data)

Neural signals can significantly influence cancer prognosis. However, how cancer cells may proactively modulate the nervous system to benefit their own survival is incompletely understood. In this study, we report an overlapping pattern of brain responses, including that in the paraventricular nucleus of the hypothalamus, in multiple mouse models of peripheral cancers. A multi-omic screen then identifies leukemia inhibitory factor (LIF) and galectin-3 (Gal3) as the key cytokines released by those cancer cell types triggering brain activation. Importantly, increased plasma levels of these two cytokines are observed in patients with different cancers. We further demonstrate that the pharmacologic or genetic blockage of cancer cell-derived LIF or Gal3 signals abolishes the brain responses and strongly inhibits tumor growth. In addition, ablation of peripheral sympathetic actions can similarly restore antitumor immunity. These results have elucidated a novel, shared mechanism of multiple cancer cell types hijacking the nervous system to promote tumor progression.