Schultze J L, Vonderheide R H
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Trends Immunol. 2001 Sep;22(9):516-23. doi: 10.1016/s1471-4906(01)02015-4.
Clinically successful specific cancer immunotherapy depends on the identification of tumor-rejection antigens (Ags). Historically, tumor Ags have been identified by analyzing either T-cell or antibody responses of cancer patients against the autologous cancer cells. The unveiling of the sequence of the human genome, improved bioinformatics tools and optimized immunological analytical tools have made it possible to screen any given protein for immunogenic epitopes. Overexpressed genes in cancer can be identified by gene-expression profiling; immunogenic epitopes can be predicted based on HLA-binding motifs; candidate peptides can be identified by mass spectrometry of tumor-cell-derived HLA molecules; and peptide-specific T cells can be qualitatively and quantitatively analyzed at the single-cell level using ELISPOT and tetramer technologies. Here, we suggest that, based on these advancements, a new class of tumor Ags can be identified by directly linking cancer genomics to cancer immunology and immunotherapy.
临床上成功的特异性癌症免疫疗法依赖于肿瘤排斥抗原（Ags）的识别。从历史上看，肿瘤抗原是通过分析癌症患者针对自体癌细胞的T细胞或抗体反应来识别的。人类基因组序列的公布、改进的生物信息学工具和优化的免疫分析工具使得筛选任何给定蛋白质的免疫原性表位成为可能。癌症中过表达的基因可通过基因表达谱分析来识别；免疫原性表位可基于HLA结合基序进行预测；候选肽可通过肿瘤细胞来源的HLA分子的质谱分析来识别；并且可以使用ELISPOT和四聚体技术在单细胞水平上对肽特异性T细胞进行定性和定量分析。在此，我们认为，基于这些进展，可以通过将癌症基因组学与癌症免疫学及免疫疗法直接联系起来，识别出一类新的肿瘤抗原。
