ABSTRACT Introduction Intrahepatic cholangiocarcinoma (ICC) is an aggressive type of malignancy. Recent advancements have highlighted the importance of the tumor immune microenvironment in therapeutic responses and prognosis. However, the lack of a mouse‐derived ICC cell line and current mouse models limit explorations of the TME in ICC. Therefore, establishing suitable preclinical models is critical. Methods In the present study, an ICC mouse model was established using hydrodynamic transfection. Primary ICC cells were isolated, purified, and cultured in the liver tissues of these mice. Cellular behaviors, molecular characterization, and genetic profiles were evaluated in vitro. The tumorigenic and metastatic potential of the cells was determined in vivo. Drug sensitivity was tested using organoids and micro‐dissected tumor tissues 3D models. Results An ICC mouse model was successfully established based on pathological identification. Characterization confirmed that the MCA23 cell line was of ICC origin and maintained the morphological and molecular features of the primary tumor. The cells exhibited robust proliferative, migratory, and invasive capabilities, enabling the rapid formation of syngeneic tumors and metastases that were highly similar to the primary tumor. Genetic analysis revealed that the cell line was a new mouse‐derived cell line with cancer cell‐karyotype characteristics. Drug testing revealed varied responses to commonly used clinical chemotherapeutics for MCA23 tumors and metastases. Conclusion MCA23 cell line provides a valuable experimental model for studying ICC pathogenesis, progression, metastasis, and drug‐resistance mechanisms. This model holds considerable promise for investigating the tumor immune microenvironment and potential immunotherapeutic approaches for advanced ICC.
He et al. (Thu,) studied this question.