Klevorn Lauryn E, Teague Ryan M
Saint Louis University School of Medicine, Molecular Microbiology and Immunology Department, 1100 South Grand Boulevard, St Louis, MO 63104, USA.
Saint Louis University School of Medicine, Molecular Microbiology and Immunology Department, 1100 South Grand Boulevard, St Louis, MO 63104, USA; Alvin J. Siteman NCI Comprehensive Cancer Center, St Louis, MO, USA.
Trends Immunol. 2016 Jun;37(6):354-363. doi: 10.1016/j.it.2016.03.010. Epub 2016 Apr 19.
Early experiments in mice predicted the success of checkpoint blockade immunotherapy in cancer patients. However, these same animal studies failed to accurately predict many of the limitations and toxicities of treatment. One of the likely reasons for this discrepancy is the nearly universal use of young healthy mice, which stand in stark contrast to diverse patient populations varying in age, weight, diet, and hygiene. Because these variables impact immunity and metabolism, they also influence outcomes during immunotherapy and should be incorporated into the study design of preclinical experiments. Here, we discuss recent findings that highlight how efficacy and toxicity of cancer immunotherapy are affected by patient variation, and how distinct host environments can be better modeled in animal studies.
早期在小鼠身上进行的实验预测了检查点阻断免疫疗法在癌症患者中的成功。然而,这些相同的动物研究未能准确预测治疗的许多局限性和毒性。这种差异的一个可能原因是几乎普遍使用年轻健康的小鼠,这与年龄、体重、饮食和卫生状况各不相同的多样化患者群体形成鲜明对比。由于这些变量会影响免疫和代谢,它们也会影响免疫治疗期间的结果,因此应纳入临床前实验的研究设计中。在这里,我们讨论了最近的研究结果,这些结果突出了癌症免疫疗法的疗效和毒性如何受到患者差异的影响,以及如何在动物研究中更好地模拟不同的宿主环境。