Ebiomedicine: a new type of natural small molecule regulatory immune remodeling tumor microenvironment for the treatment of liver cancer

HCC is the second leading cause of cancer death in the world, which seriously affects people's health Tumor cells and stromal cells (endothelial cells, fibroblasts, a variety of immune cells, etc.) interact in tumor microenvironment to jointly regulate tumor growth and progression Tumor associated macrophages, as one of the important inflammatory cells, participate in the process of tumor development, invasion and metastasis, and are closely related to tumor angiogenesis and immunosuppression Targeting tumor related macrophages in tumor microenvironment and remolding tumor microenvironment has become a research hotspot in the field of tumor therapy Targeting CCR2 regulates the recruitment of macrophages controlled by CCL2 / CCR2 signaling pathway in the treatment of liver cancer (source: eBIO medicine), which is related to the initiation and progression of various liver diseases, including liver cancer, making it a target for the treatment of liver cancer At present, CCR2 antagonists are still in the development stage of preclinical and clinical trials Due to the lack of selectivity for other chemokine receptors, species differences in drug development and poor drug metabolism, there is still a lack of mature CCR2 antagonists Wang Hui's team from Shanghai Academy of Biological Sciences found a natural CCR2 antagonist (No 747) extracted from Abies georgei, which can inhibit liver cancer by relieving the immunosuppressive microenvironment caused by tumor-related macrophages, and increase the therapeutic effect of low-dose sorafenib Kaempferol (source: Wikipedia) The researchers screened a natural CCR2 antagonist 747, and confirmed its good selectivity, sensitivity and safety through in vitro and in vivo experiments It can inhibit the development of liver cancer by preventing tumor macrophages from infiltrating and differentiating into tumor suppressive phenotypes, increasing the number of CD8 + T cells and enhancing the killing ability of CD8 + T cells, and as a combination of immunomodulators Low dose of sorafenib can enhance the therapeutic effect of sorafenib To sum up, this study found a new natural CCR2 antagonist named 747, which provides a new perspective for the development of CCR2 antagonists, and indicates that the combination of immunomodulators and chemotherapy drugs may be a new strategy for the treatment of liver cancer Paper link: http://www.ebiomedicine.com/article/s2352-3964 (17) 30287-6 / Fulltext