Wang Ena, Panelli Monica C, Marincola Francesco M
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Curr Opin Immunol. 2005 Aug;17(4):423-7. doi: 10.1016/j.coi.2005.05.007.
Clinical trials of tumor-antigen-specific immunization have clearly shown that immune-mediated tumor rejection requires more than simple T cell-target cell interactions. In vivo generation of tumor-specific T cells is one of a series of steps necessary for the induction of clinically relevant immune responses. In recent years, high-throughput functional genomics exposed the complexity of tumor immune biology, which underlies the kaleidoscopic array of variables associated with cancer instability and immunogenetic variability in humans. In the quest to understand immune rejection, hypothesis-driven approaches have failed to take into account the intricacy of human pathology by relying mostly on hypotheses derived from experimental models rather than direct clinical observation. Future investigations should reframe scientific thinking when applied to humans, utilizing descriptive tools to generate novel hypotheses relevant to human disease.
肿瘤抗原特异性免疫的临床试验已清楚表明，免疫介导的肿瘤排斥反应需要的不仅仅是简单的T细胞与靶细胞相互作用。肿瘤特异性T细胞的体内生成是诱导临床相关免疫反应所需的一系列步骤之一。近年来，高通量功能基因组学揭示了肿瘤免疫生物学的复杂性，这是与人类癌症不稳定性和免疫遗传学变异性相关的一系列变量的基础。在试图理解免疫排斥反应的过程中，假设驱动的方法大多依赖于从实验模型得出的假设，而非直接的临床观察，未能考虑到人类病理学的复杂性。未来的研究在应用于人类时应重新构建科学思维，利用描述性工具来生成与人类疾病相关的新假设。
