Zhou Yulai, Zhang Xiangyang, Gao Yan, Peng Yinghui, Liu Ping, Chen Yihong, Guo Cao, Deng Gongping, Ouyang Yanhong, Zhang Yan, Han Ying, Cai Changjing, Shen Hong, Gao Le, Zeng Shan
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Department of Microbiology, Immunology & Molecular Genetics, University of Texas Long School of Medicine, UT Health Science Center, San Antonio, TX 78229, USA.
iScience. 2024 Jun 20;27(7):110318. doi: 10.1016/j.isci.2024.110318. eCollection 2024 Jul 19.
Colorectal cancer (CRC) exhibits significant heterogeneity, impacting immunotherapy efficacy, particularly in immune desert subtypes. Neuromedin U receptor 1 (NMUR1) has been reported to perform a vital function in immunity and inflammation. Through comprehensive multi-omics analyses, we have systematically characterized NMUR1 across various tumors, assessing expression patterns, genetic alterations, prognostic significance, immune infiltration, and pathway associations at both the bulk sequencing and single-cell scales. Our findings demonstrate a positive correlation between NMUR1 and CD8 T cell infiltration, with elevated NMUR1 levels in CD8 T cells linked to improved immunotherapy outcomes in patients with CRC. Further, we have validated the NMUR1 expression signature in CRC cell lines and patient-derived tissues, revealing its interaction with key immune checkpoints, including lymphocyte activation gene 3 and cytotoxic T-lymphocyte-associated protein 4. Additionally, NMUR1 suppression enhances CRC cell proliferation and invasiveness. Our integrated analyses and experiments open new avenues for personalized immunotherapy strategies in CRC treatment.
结直肠癌（CRC）表现出显著的异质性，影响免疫治疗疗效，尤其是在免疫“沙漠”亚型中。据报道，神经介素U受体1（NMUR1）在免疫和炎症中发挥重要作用。通过全面的多组学分析，我们系统地表征了NMUR1在各种肿瘤中的特征，在 bulk 测序和单细胞水平上评估了其表达模式、基因改变、预后意义、免疫浸润和通路关联。我们的研究结果表明，NMUR1与CD8 T细胞浸润呈正相关，CD8 T细胞中NMUR1水平升高与CRC患者免疫治疗效果改善有关。此外，我们在CRC细胞系和患者来源的组织中验证了NMUR1表达特征，揭示了其与关键免疫检查点的相互作用，包括淋巴细胞激活基因3和细胞毒性T淋巴细胞相关蛋白4。此外，NMUR1抑制增强了CRC细胞的增殖和侵袭性。我们的综合分析和实验为CRC治疗中的个性化免疫治疗策略开辟了新途径。
