Cancer Immunotherapy: Historical Perspective of a Clinical Revolution and Emerging Preclinical Animal Models.
Cancer Immunotherapy: Historical Perspective of a Clinical Revolution and Emerging Preclinical Animal Models.
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DOI：
10.3389/fimmu.2017.00829
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发表时间：
2017
影响因子：
7.3
通讯作者：
Paust S
中科院分区：
文献类型：
--
作者：
Decker WK;da Silva RF;Sanabria MH;Angelo LS;Guimarães F;Burt BM;Kheradmand F;Paust S
在上个世纪之交，新兴的医学肿瘤学领域选择了细胞毒性的癌症治疗方法，而不是以免疫为中心的方法，当时还没有证据支持这两种范式。今天，近120年的数据已经确定，（a）即使是最好的细胞毒性方案也很少治愈晚期恶性肿瘤，（B）补充和增强现有抗肿瘤免疫应答的策略提供了最大的机会来增强癌症的持久缓解。尽管这些范例今天被广泛接受，但免疫系统识别和对抗癌症的能力在20世纪的大部分时间里都是一个极具争议的话题。为什么这一现代范式的中流砥柱在如此长的一段时间里既可疑又有争议，这是一个值得坦率讨论的相当有趣的话题。在此，我们回顾文献，以确定和描述的分水岭事件，最终导致接受免疫治疗作为一个可行的方案治疗恶性肿瘤。除了注意到重要的临床发现外，我们还专注于研究里程碑和啮齿动物和狗的关键模型系统的开发，包括允许开发患者来源的异种移植物的先进建模技术。总之，它们的使用将进一步加深我们对癌症生物学和肿瘤免疫学的理解，允许更快地评估新方法的有效性和安全性，并最终提供更快的过渡。
At the turn of the last century, the emerging field of medical oncology chose a cytotoxic approach to cancer therapy over an immune-centered approach at a time when evidence in support of either paradigm did not yet exist. Today, nearly 120 years of data have established that (a) even the best cytotoxic regimens only infrequently cure late-stage malignancy and (b) strategies that supplement and augment existing antitumor immune responses offer the greatest opportunities to potentiate durable remission in cancer. Despite widespread acceptance of these paradigms today, the ability of the immune system to recognize and fight cancer was a highly controversial topic for much of the twentieth century. Why this modern paradigmatic mainstay should have been both dubious and controversial for such an extended period is a topic of considerable interest that merits candid discussion. Herein, we review the literature to identify and describe the watershed events that ultimately led to the acceptance of immunotherapy as a viable regimen for the treatment of neoplastic malignancy. In addition to noting important clinical discoveries, we also focus on research milestones and the development of critical model systems in rodents and dogs including the advanced modeling techniques that allowed development of patient-derived xenografts. Together, their use will further our understanding of cancer biology and tumor immunology, allow for a speedier assessment of the efficacy and safety of novel approaches, and ultimately provide a faster bench to beside transition.