Subcutaneous vs. orthotopic tumor models: A comparative assessment

AACR 2024 -- The failure of murine tumor models to adequately simulate the native biological milieu and tissue architecture of human malignancies, has fomented much discourse surrounding the exigencies of bench to bedside translation. Orthotopic (OT) models, which are generated by the engraftment of tumor cells or fragments into recipient organs of the same histotype from which they were derived, has the advantage of recapitulating the appropriate vasculature, as well as the cellular and stromal components as the site of origin. OT models therefore represent a more disease-relevant preclinical approach compared to their subcutaneous (SC) counterparts, as they more reliably preserve the intrinsic infrastructure and complexities of patient tumors in situ. To demonstrate the significance of the anatomical site of the tumor, we performed a comparative assessment of SC and OT CT26-luc and MC38-luc murine colon carcinoma models using flow cytometry, in the context of treatment with various immunotherapeutic agents.