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.

中文翻译：

---

IL6调节肿瘤微环境的免疫状态，以促进结直肠癌细胞的转移定植。

关于大肠癌中肝转移与宿主免疫状态之间的关系还不清楚。在这项研究中，我们发现IL6（一种在荷瘤状态下产生的促炎细胞因子）可促进结肠癌细胞的转移性定植，并具有抗肿瘤免疫功能异常。在IL6缺陷小鼠体内，CT26细胞在肝脏的转移定植减少，并且CD8 + T细胞的抗肿瘤效应功能以及CD11c +树突状细胞的IL12产生在体内得以增强。IL6缺陷小鼠表现出增强的IFN-AR1介导的I型干扰素信号传导，上调PD26和PD-L1和MHC I类在CT26细胞上的表达。体内注射抗PD-L1有效抑制了Il6--/-小鼠中CT26细胞的转移定植，但不适用于Il6 + / +小鼠。最后，我们证实，在原发性肿瘤中IL6表达低的结直肠癌患者可延长无病生存期。这些发现表明，IL6可能通过改善宿主免疫力成为治疗结直肠癌转移的有希望的靶标。