Preclinical immunotherapy research relies heavily on animal tumor models, which can be broadly classified into four categories: genetically engineered, carcinogen-induced, spontaneous, and humanized transplantation platforms. While these systems mimic tumorigenesis, immune-microenvironment interactions, and therapeutic responses, their clinical translational utility is limited by species differences, incomplete immune reconstitution, and significant ethical concerns. This review synthesizes current approaches, systematically catalogs their respective strengths and limitations, and proposes integrated solutions that incorporate multi-omics datasets, artificial intelligence modeling, standardized protocols, and international consortia. Future research should prioritize the development of next-generation humanized platforms and virtual digital tumor models, and accelerate clinical translation through rigorous cross-species validation.
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