Hashimoto M, Konda JD, Perrino S, et al. - Findings show that pancreatic ductal adenocarcinoma (PDAC) metastases can be significantly therapeutically benefitted from a combinatorial immunotherapy based on dual targeting of the pro-metastatic immune microenvironment of the liver via IGF blockade, on one hand, and reversing T cell exhaustion on the other.

• Murine models of aggressive PDAC with liver metastases were treated with the IGF-Trap, an inhibitor of type 1 insulin like growth factor receptor (IGF-IR) signaling.

• As a result, the local, immunosuppressive tumor microenvironment in the liver was profoundly altered, which curtailed the recruitment of myeloid derived suppressor cells, reversed innate immune cell polarization and inhibited metastatic expansion.

• Significantly, growth of experimental PDAC liver metastases was reduced due to immunotherapy with anti PD-1 antibodies, this effect was enhanced when combined with IGF-Trap treatment, leading to further potentiation of a T cell response.