IL6 modulates the immune status of the tumor microenvironment to facilitate metastatic colonization of colorectal cancer cells

It is unknown as to how liver metastases are correlated with host immune status in colorectal cancer. In this study, we found that IL-6, a proinflammatory cytokine produced in tumor-bearing states, promotes the metastatic colonization of colon cancer cells in association with dysfunctional anti-tumor immunity. In IL-6-deficient mice, metastatic colonization of CT26 cells in the liver was reduced, and the anti-tumor effector function of CD8+ T cells as well as IL-12 production by CD11c+ dendritic cells were augmented in vivo. Furthermore, IL-6-deficient mice exhibited enhanced IFNAR1- mediated type I interferon signaling, which upregulated PD-L1 and MHC class I expression on CT26 cells. In vivo injection of anti-PD-L1 antibody effectively suppressed the metastatic colonization of CT26 cells in Il6-/- but not Il6+/+ mice. Finally, we confirmed that colorectal cancer patients with low IL-6 levels in their primary tumors showed prolonged disease-free survival. These findings suggest IL-6 may be a promising target for the treatment of metastasis in colorectal cancers by improving host immunity