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Supplementary Figures 8-9 from IL6 Modulates the Immune Status of the Tumor Microenvironment to Facilitate Metastatic Colonization of Colorectal Cancer Cells

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posted on 2023-04-04, 00:42 authored by Yujiro Toyoshima, Hidemitsu Kitamura, Huihui Xiang, Yosuke Ohno, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Toshiya Kamiyama, Mishie Tanino, Akinobu Taketomi

Supplementary Figures 8-9

Funding

Japan Society for the Promotion of Science

Institute for Genetic Medicine, Hokkaido University

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ARTICLE ABSTRACT

It is unknown as to how liver metastases are correlated with host immune status in colorectal cancer. In this study, we found that IL6, a proinflammatory cytokine produced in tumor-bearing states, promoted the metastatic colonization of colon cancer cells in association with dysfunctional antitumor immunity. In IL6-deficient mice, metastatic colonization of CT26 cells in the liver was reduced, and the antitumor effector function of CD8+ T cells, as well as IL12 production by CD11c+ dendritic cells, were augmented in vivo. IL6-deficient mice exhibited enhanced IFN-AR1–mediated type I interferon signaling, which upregulated PD-L1 and MHC class I expression on CT26 cells. In vivo injection of anti–PD-L1 effectively suppressed the metastatic colonization of CT26 cells in Il6−/− but not in Il6+/+ mice. Finally, we confirmed that colorectal cancer patients with low IL6 expression in their primary tumors showed prolonged disease-free survival. These findings suggest that IL6 may be a promising target for the treatment of metastasis in colorectal cancers by improving host immunity.

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