Mouse models in oncoimmunology

Key Points The cell-autonomous conception of cancer has been progressively substituted by a view in which interactions of malignant and stromal elements, including immune cells, condition the tumour microenvironment. Transplantable models of mouse cancers implanted in histocompatible, immunocompetent mice have spurred the development of immune checkpoint blockers, as well as the discovery that chemotherapy- and radiotherapy-induced immunogenic cell death stimulates therapeutically relevant anticancer immune responses. Carcinogen-induced models have been instrumental for the discovery of the major principles of anticancer immunoediting, including elimination, equilibrium and escape. Genetically engineered mouse models (GEMMs) are providing fundamental insights into tissue- and context-dependent mechanisms of immune recognition and suppression. Modern genome-editing technologies offer the possibility of exchanging individual mouse genes or entire loci with their human equivalents with the possibility of introducing human elements of the immune and haematological systems into a progressively 'humanized' environment. The combination of immunodeficiencies that affect the mouse immune system, the humanization of the mouse genome by knock in of human genes or loci and the transplantation of human immune cells and tumours provides ever more refined models for oncoimmunology. In this Review, Zitvogel et al . describe the mouse models of transplantable, carcinogen-induced and genetically engineered tumours that have laid the foundations of oncoimmunology. Fundamental cancer research and the development of efficacious antineoplastic treatments both rely on experimental systems in which the relationship between malignant cells and immune cells can be studied. Mouse models of transplantable, carcinogen-induced or genetically engineered malignancies — each with their specific advantages and difficulties — have laid the foundations of oncoimmunology. These models have guided the immunosurveillance theory that postulates that evasion from immune control is an essential feature of cancer, the concept that the long-term effects of conventional cancer treatments mostly rely on the reinstatement of anticancer immune responses and the preclinical development of immunotherapies, including currently approved immune checkpoint blockers. Specific aspects of pharmacological development, as well as attempts to personalize cancer treatments using patient-derived xenografts, require t