The humanized mouse: Emerging translational potential

The humanized mouse (HM) has emerged as a valuable animal model in cancer research. Engrafted with components of a human immune system and subsequently implanted with tumor tissue from cell lines or in the form of patient-derived xenografts, the HM provides a unique platform in which the tumor microenvironment (TME) can be evaluated in vivo. This model may also be beneficial in the assessment of potential cancer treatments including immune checkpoint inhibitors. However, to maximize its utility, researchers need to understand the critical factors necessary to ensure that the tumor immune interactions in the HM are representative of those within cancer patients. In most current HM models, the human T cells residing in the HM are educated in a murine thymus, allogeneic to implanted tumor tissue, and/or alloreactive to mouse tissues, making their interaction and reactivity with tumor cells suspect. There are several strategies underway to harmonize the immune-tumor environment in the HM. Once the essential components of the HM-tumor TME interface have been identified and understood, the HM model will permit not only the discovery of effective immunotherapy treatments, but it can be used to predict patient responses to great clinical benefit.