Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice

Cancer immunotherapy has brought significant clinical benefits to numerous patients with malignant disease. However, only a fraction of patients experiences complete and durable responses to currently available immunotherapies. This highlights the need for more effective immunotherapies, combination treatments and predictive biomarkers. The molecular properties of a tumor, intratumor heterogeneity and the tumor immune microenvironment decisively shape tumor evolution, metastasis and therapy resistance and are therefore key targets for precision cancer medicine. Humanized mice that support the engraftment of patient-derived tumors and recapitulate the human tumor immune microenvironment of patients represent a promising preclinical model to address fundamental questions in precision immuno-oncology and cancer immunotherapy. In this review, we provide an overview of next-generation humanized mouse models suitable for the establishment and study of patient-derived tumors. Furthermore, we discuss the opportunities and challenges of modeling the tumor immune microenvironment and testing a variety of immunotherapeutic approaches using human immune system mouse models.

Automated summary

Cancer immunotherapy has benefited many patients with malignant disease, but only a small fraction of patients respond completely and durably. More effective immunotherapies, combination treatments, and predictive biomarkers are needed. The molecular properties of a tumor, intratumor heterogeneity, and the tumor immune microenvironment play important roles in tumor evolution, metastasis, and therapy resistance. Humanized mouse models that replicate the human tumor immune microenvironment are promising for studying precision immuno-oncology and testing immunotherapeutic approaches.