Tumor Microenvironment Varies under Different TCMZHENGModels and Correlates with Treatment Response to Herbal Medicine

摘要

In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation orZHENG. The cornerstone of TCM,ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of theZHENGremains unclear. In this study, we established mouse xenograft pancreatic cancer models withShi-Re(Dampness-Heat),Pi-Xu(Spleen-Deficiency), orXue-Yu(Blood-Stasis)ZHENG, which are regarded as the three majorZHENGs in pancreatic cancer. We found that tumors of the differentZHENGmodels exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. TheZHENGmodel type also significantly influenced tumor growth, and administration of herbal medicine to theZHENGmodel modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCMZHENGin pancreatic cancer.