Yao Pengju, Gao Mingjie, Hu Weiyi, Wang Jiahao, Wang Yuhao, Wang Qingsong, Ji Jianguo
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.
Pharmacol Res. 2024 Jun;204:107209. doi: 10.1016/j.phrs.2024.107209. Epub 2024 May 11.
Considerable progress has recently been made in cancer immunotherapy, including immune checkpoint blockade, cancer vaccine, and adoptive T cell methods. The lack of effective targets is a major cause of the low immunotherapy response rate in colorectal cancer (CRC). Here, we used a proteogenomic strategy comprising immunopeptidomics, whole exome sequencing, and 16 S ribosomal DNA sequencing analyses of 8 patients with CRC to identify neoantigens and bacterial peptides that can serve as antitumor targets. This study directly identified several personalized neoantigens and bacterial immunopeptides. Immunoassays showed that all neoantigens and 5 of 8 bacterial immunopeptides could be recognized by autologous T cells. Additionally, T cell receptor (TCR) αβ sequencing revealed the TCR repertoire of epitope-reactive CD8 T cells. Functional studies showed that T cell receptor-T (TCR-T) could be activated by epitope pulsed lymphoblastoid cells. Overall, this study comprehensively profiled the CRC immunopeptidome, revealing several neoantigens and bacterial peptides with potential to serve as immunotherapy targets in CRC.
近年来，癌症免疫疗法取得了显著进展，包括免疫检查点阻断、癌症疫苗和过继性T细胞疗法。缺乏有效靶点是结直肠癌（CRC）免疫治疗反应率低的主要原因。在此，我们采用了一种蛋白质基因组学策略，对8例CRC患者进行免疫肽组学、全外显子组测序和16S核糖体DNA测序分析，以鉴定可作为抗肿瘤靶点的新抗原和细菌肽。本研究直接鉴定出了几种个性化新抗原和细菌免疫肽。免疫分析表明，所有新抗原和8种细菌免疫肽中的5种均可被自体T细胞识别。此外，T细胞受体（TCR）αβ测序揭示了表位反应性CD8 T细胞的TCR库。功能研究表明，表位脉冲淋巴母细胞可激活T细胞受体-T（TCR-T）。总体而言，本研究全面分析了CRC免疫肽组，揭示了几种有潜力作为CRC免疫治疗靶点的新抗原和细菌肽。
