Kiyotani Kazuma, Toyoshima Yujiro, Nakamura Yusuke
Project for Immunogenomics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
J Hum Genet. 2021 Sep;66(9):901-907. doi: 10.1038/s10038-021-00950-w. Epub 2021 Jun 30.
Recent advances in next-generation sequencing technologies have led to significant improvements in cancer genomic research and cancer treatment. Through the use of comprehensive cancer genome data, precision medicine has become more of a reality; albeit, at present, only ~10-15% of patients can benefit from current genomic testing practices. Improvements in cancer genome analyses have contributed to a better understanding of antitumor immunity and have provided solutions for targeting highly cancer-specific neoantigens generated from somatic mutations in individual patients. Since then, numerous studies have demonstrated the importance of neoantigens and neoantigen-reactive T cells in the tumor microenvironment and how their presence influences the beneficial responses associated with various cancer immunotherapies, including immune checkpoint inhibitor therapy. Indeed, cancer immunotherapies that explicitly target neoantigens specific to individual cancer patients would lead to the ultimate form of cancer precision medicine. For this to be realized, several issues would need to be overcome, including the accurate prediction and selection of neoantigens that can induce cytotoxic T cells in individual patients. The precise prediction of target neoantigens will likely accelerate the development of personalized immunotherapy including cancer vaccines and T-cell receptor-engineered T-cell therapy for patients with cancer.
新一代测序技术的最新进展已使癌症基因组研究和癌症治疗取得了显著改善。通过使用全面的癌症基因组数据,精准医学已更接近现实;尽管目前只有约10%-15%的患者能从当前的基因组检测实践中受益。癌症基因组分析的改进有助于更好地理解抗肿瘤免疫,并为靶向个体患者体细胞突变产生的高度癌症特异性新抗原提供了解决方案。从那时起,大量研究证明了新抗原和新抗原反应性T细胞在肿瘤微环境中的重要性,以及它们的存在如何影响与各种癌症免疫疗法(包括免疫检查点抑制剂疗法)相关的有益反应。事实上,明确靶向个体癌症患者特异性新抗原的癌症免疫疗法将带来癌症精准医学的终极形式。要实现这一点,需要克服几个问题,包括准确预测和选择能在个体患者中诱导细胞毒性T细胞的新抗原。精确预测靶新抗原可能会加速个性化免疫疗法的发展,包括针对癌症患者的癌症疫苗和T细胞受体工程化T细胞疗法。