Harnessing the Pre-metastatic Niche Macrophages through the Induction of Trained Immunity to control Metastasis.

We demonstrate that a natural compund B-Glucan (WGP) can induce training of macrophages by upregulating the Sphingolipid biosynthesis pathway and more specifically, the accumulation of S1P, resulting in mitochondrial fission in macrophages. These trained macrophages upon re-stimulation with tumor cells or tumor-derived factors showed increased responsiveness by increased pro-inflammatory cytokine production, increased phagocytosis and cytotoxicity. In vivo training of mice with WGP resulted in the training of Lung Interstitial macrophages and controlled the metastasis to the lungs. We employed different in vivo models of Lung metastasis to demonstrate that training of the pre-metastatic lung interstitial macrophages with a natural compound, B-Glucan, induces the control of cancer metastasis to the lungs.