人源免疫重建PDX模型构建及其在肿瘤免疫治疗中的应用进展

Application progress of humanized patient-derived xenograft models in tumor immunotherapy

免疫治疗已成为肿瘤治疗领域最具潜力的手段之一。由于肿瘤存在高度异质性等特点,导致免疫治疗响应率偏低,疗效有限。因此,迫切需要具有预测性的临床前模型,用于推动合理、安全的免疫治疗策略开发。传统体内、外肿瘤研究模型受限于人源免疫系统的缺失。因此,构建同时具有人源免疫系统和肿瘤的研究模型成为热点。将患者来源肿瘤移植入人源免疫系统重建小鼠体内肿瘤、免疫双人源化模型,具有可重现人体内免疫细胞与肿瘤间相互作用的优势,成为生理和病理条件下模拟人体肿瘤免疫治疗疗效的新模型。本文主要对多种类型人源化免疫重建PDX模型构建、优缺点及其在肿瘤免疫治疗研究中的最新应用进展进行综述。

Immunotherapy may be the most effective breakthrough in cancer therapy.However,its clinical efficacy and response rate are impeded by the pronounced intratumoural heterogeneity.The development and establishment of predictive models of novel immunotherapeutic strategies are urgently needed.Conventional in vitro and in vivo models are limited by their inability to mimic the human immune system.In contrast,a humanized patient-derived xenograft(PDX)model can reproduce the interactions between the human immune system and the tumor microenvironment.The PDX model is a more suitable and applicable research model for human tumor immunotherapy under physiological and pathological conditions.Here,we review the construction methods,advantages,and application progress of humanized immune system PDX models for tumor immunotherapy.