RESUMO
Background: The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown. Methods: We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages. Results: Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice. Conclusions: We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC.
RESUMO
The human liver fulfills several vital tasks daily and possesses an impressive ability to self-regenerate. However, the capacity of this self-healing process can be exhausted by a variety of different liver diseases, such as alcoholic liver damage, viral hepatitis, or hepatocellular carcinoma. Over time, all these diseases generally lead to progressive liver failure that can become fatal if left untreated. Thus, a great effort has been directed towards the development of innovative therapies. The most recently discovered therapies often involve modifying the patient's immune system to enhance a beneficial immune response. Current data suggest that, among others, the cytokine IL-22 might be a promising therapeutical candidate. IL-22 and its endogenous antagonist, IL-22BP, have been under thorough scientific investigation for nearly 20 years. While IL-22 is mainly produced by TH22 cells, ILC3s, NKT cells, or γδ T cells, sources of IL-22BP include dendritic cells, eosinophils, and CD4+ cells. In many settings, IL-22 was shown to promote regenerative potential and, thus, could protect tissues from pathogens and damage. However, the effects of IL-22 during carcinogenesis are more ambiguous and depend on the tumor entity and microenvironment. In line with its capabilities of neutralizing IL-22 in vivo, IL-22BP possesses often, but not always, an inverse expression pattern compared to its ligand. In this comprehensive review, we will summarize past and current findings regarding the roles of IL-22 and IL-22BP in liver diseases with a particular focus on the leading causes of advanced liver failure, namely, liver infections, liver damage, and liver malignancies.