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Mouse models in oncoimmunology

机译:肿瘤免疫学中的小鼠模型

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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 the development of mouse models in which murine genes and cells are replaced with their human equivalents. Such ' humanized' mouse models are being progressively refined to characterize the leukocyte subpopulations that belong to the innate and acquired arms of the immune system as they infiltrate human cancers that are subjected to experimental therapies. We surmise that the ever-advancing refinement of murine preclinical models will accelerate the pace of therapeutic optimization in patients.
机译:基础癌症研究和有效抗肿瘤治疗的发展均依赖于实验系统,在该系统中可以研究恶性细胞与免疫细胞之间的关系。可移植的,致癌物诱导的或基因工程的恶性肿瘤的小鼠模型(每种都有其独特的优势和困难)奠定了肿瘤免疫学的基础。这些模型指导了免疫监视理论,该理论假定逃避免疫控制是癌症的基本特征,即传统癌症治疗的长期效果主要取决于抗癌免疫反应的恢复和免疫疗法的临床前开发,包括目前批准的免疫检查点阻滞剂。药理学发展的特定方面以及尝试使用源自患者的异种移植来个性化癌症治疗,都需要开发小鼠模型,在该模型中,鼠类基因和细胞被其人类等价物所替代。此类“人源化”小鼠模型正在逐步完善,以表征属于免疫系统先天和后天分支的白细胞亚群,因为它们渗入了接受实验疗法的人类癌症。我们推测,不断完善的小鼠临床前模型将加快患者治疗优化的步伐。

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