尽管嵌合抗原受体（CAR）T细胞疗法在治疗某些血液系统恶性肿瘤方面取得了显著的成功，但仍面临着优化CAR设计和细胞产品、提高反应率、延长缓解期、减少毒性及将该治疗模式扩展到其他癌症类型的挑战。多维组学分析数据，包括基因组学、表观基因组学、转录组学、T细胞受体类型分布分析、蛋白质组学、代谢组学和/或微生物组学，为解析CAR T细胞的复杂和动态的多因素表型、过程和反应提供了独特的机会，同时还可以发现新的肿瘤靶点和耐药途径。在本综述中，我们总结了用于推动我们对CAR T细胞疗法机制理解的多维细胞和分子分析技术。此外，我们讨论了当前应用和潜在策略，利用多组学数据标识最佳靶抗原和其他可利用于增强CAR T细胞治疗的抗肿瘤活性并减少毒性的分子特征。确实，充分利用多组学数据将为CAR T细胞治疗的生物学提供新的视角，进一步加速具有改进的疗效和安全性能的产品的开发，并使临床医生更好地预测和监测患者的反应。©2023年Springer Nature有限公司。

Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing CAR designs and cell products, improving response rates, extending the durability of remissions, reducing toxicity and broadening the utility of this therapeutic modality to other cancer types. Data from multidimensional omics analyses, including genomics, epigenomics, transcriptomics, T cell receptor-repertoire profiling, proteomics, metabolomics and/or microbiomics, provide unique opportunities to dissect the complex and dynamic multifactorial phenotypes, processes and responses of CAR T cells as well as to discover novel tumour targets and pathways of resistance. In this Review, we summarize the multidimensional cellular and molecular profiling technologies that have been used to advance our mechanistic understanding of CAR T cell therapies. In addition, we discuss current applications and potential strategies leveraging multi-omics data to identify optimal target antigens and other molecular features that could be exploited to enhance the antitumour activity and minimize the toxicity of CAR T cell therapy. Indeed, fully utilizing multi-omics data will provide new insights into the biology of CAR T cell therapy, further accelerate the development of products with improved efficacy and safety profiles, and enable clinicians to better predict and monitor patient responses.© 2023. Springer Nature Limited.