Ccl9, also known as chemokine (C-C motif) ligand 9, is a chemokine that plays a crucial role in leukocyte chemotaxis and tissue inflammation regulation [4]. It is involved in multiple signaling pathways related to immune responses and disease development. Genetic models, especially KO/CKO mouse models, have been instrumental in understanding its functions.

In a murine model of colon cancer, overexpression of Ccl9 in CT26.CL25 colon cancer cells led to a decline in tumor growth in vivo, with microarray analysis of tumor tissues showing upregulation of immune system-related genes, suggesting its anti-proliferative function via interaction with host immune cells [2]. In an orthotopic hepatoma mouse model, spleen-derived Ccl9 recruited myeloid-derived suppressor cells (MDSC), facilitating tumor growth, and splenectomy decreased Ccl9 levels in tumor tissue and the percentage of MDSC [3]. Blockade of Ccl9 in p48cre:KrasG12D transgenic mice attenuated pancreatic acinar-to-ductal metaplasia (ADM) structures and PanIN lesion formation, and also diminished infiltrating macrophages and MMP expression in ADM areas, indicating its role in promoting ADM through upregulation of ROS and MMPs [1].

In conclusion, Ccl9 has diverse functions in disease processes. Its role in promoting or suppressing tumor growth depends on the context. In colon cancer, it may act as a tumor suppressor, while in hepatoma and pancreatic cancer models, it promotes tumor-related processes. The study of Ccl9 using KO/CKO mouse models has provided insights into its role in cancer development, offering potential therapeutic targets for these diseases.