Research Center for Immunotherapy (FZI), Langenbeckstr. 1, Building 708, Mainz 55131, Germany.
TRON - Translational Oncology at the University Medical Center of Johannes Gutenberg University, Freiligrathstr. 12, 55131 Mainz, Germany.
Curr Opin Immunol. 2016 Apr;39:14-22. doi: 10.1016/j.coi.2015.12.001. Epub 2015 Dec 21.
Somatic mutations are important drivers of cancer development. Accumulating evidence suggests that a significant subset of mutations result in neo-epitopes recognized by autologous T cells and thus may constitute the Achilles' heel of tumor cells. T cells directed against mutations have been shown to have a key role in clinical efficacy of potent cancer immunotherapy modalities, such as adoptive transfer of autologous tumor infiltrating lymphocytes and immune checkpoint inhibitors. Whereas these findings strengthen the idea of a prominent role of neo-epitopes in tumor rejection, the systematic therapeutic exploitation of mutations was hampered until recently by the uniqueness of the repertoire of mutations ('the mutanome') in every patient's tumor. This review highlights insights into immune recognition of neo-epitopes and novel concepts for comprehensive identification and immunotherapeutic exploitation of individual mutations.
体细胞突变是癌症发展的重要驱动因素。越来越多的证据表明，大量的突变会导致自身 T 细胞识别的新表位，因此可能构成肿瘤细胞的致命弱点。针对突变的 T 细胞已被证明在有效的癌症免疫治疗模式（如自体肿瘤浸润淋巴细胞的过继转移和免疫检查点抑制剂）的临床疗效中发挥关键作用。尽管这些发现加强了新表位在肿瘤排斥中的重要作用的观点，但直到最近，由于每个患者肿瘤中的突变（“突变组”）谱的独特性，系统性地利用突变进行治疗受到了阻碍。这篇综述强调了对新表位的免疫识别的新见解，并为全面鉴定和免疫治疗利用个体突变提供了新的概念。
