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Tumor heterogeneity occurs across patients and within individual tumors, challenging truly personalized treatment. Single-cell multi-omics integrating genomics, transcriptomics, epigenomics, proteomics, and spatial omics enables single-cell, multi-layer dissection of tumor variation. The review surveys advances, highlighting impacts on tumor heterogeneity understanding, immune escape, treatment resistance, minimal residual disease monitoring, and neoantigen discovery, while addressing technical and analytical limitations.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/single-cell-multi-omics-in-cancer-immunotherapy-from-tumor-heterogeneity-to-personalized-precision-treatment/374723/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/single-cell-multi-omics-in-cancer-immunotherapy-from-tumor-heterogeneity-to-personalized-precision-treatment/374723.png","ImageObject",300,407,{"name":92,"@type":93},"eBook King","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the review focus on in cancer immunotherapy?","Question",{"text":112,"@type":113},"It focuses on how cancer’s complexity and tumor heterogeneity limit broad therapeutic efficacy and personalized treatment success.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What do single-cell multi-omics approaches enable at a high level?",{"text":117,"@type":113},"They enable multi-dimensional analyses (genomics, transcriptomics, epigenomics, proteomics, and spatial omics) to dissect tumor heterogeneity at single-cell resolution.",{"name":119,"@type":110,"acceptedAnswer":120},"Which applications does the review highlight for single-cell multi-omics in cancer research?",{"text":121,"@type":113},"It emphasizes understanding tumor heterogeneity, immune escape mechanisms, treatment resistance, minimal residual disease monitoring, and neoantigen discovery.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},374723,1790245972,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962088006270,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Le etal. Molecular Cancer (2025) 24:221 Molecular Cancer  \n[https://doi.org/10.1186/s12943-025-02426-3](https://doi.org/10.1186/s12943-025-02426-3)  \nREVIEW Open Access  \nSingle-cell multi-omics in cancer immunotherapy: from tumor heterogeneity to personalized precision treatment  \nJiayuan Le 1,2,3,4,5, Yating Dian 1,2,3,4,5, Deze Zhao6, Ziyu Guo 1,2,3,4,5, Zehao Luo 1,2,3,4,5, Xiang Chen 1,2,3,4,5, Furong Zeng7* and Guangtong Deng 1,2,3,4,5*  \nAbstract  \nCancer immunotherapy has revolutionized clinical oncology; however, the inherent complexity and heterogeneity of cancer present substantial challenges to achieving broad therapeutic efficacy. Tumor heterogeneity manifests not only among different patients but also within individual tumors, further complicating personalized treatment approaches. Single-cell sequencing technologies encompassing genomics, transcriptomics, epigenomics, proteomics, and spatial omics have significantly enhanced our ability to dissect tumor heterogeneity at singlecell resolution with multi-layered depth. These approaches have illuminated tumor biology, immune escape mechanisms, treatment resistance, and patient-specific immune response mechanisms, thereby substantially advancing precision oncology strategies. This review systematically examines recent advances in single-cell multi-omics technologies across various cancer research areas, emphasizing their transformative impacts on understanding tumor heterogeneity, immunotherapy, minimal residual disease monitoring, and neoantigen discovery. Additionally, we discuss current technical and analytical limitations and unresolved questions associated with single-cell technologies. We anticipate single-cell multi-omics technologies will become central to precision oncology, facilitating truly personalized therapeutic interventions.  \nKeywords Single-cell sequencing, Immunotherapy, Tumor heterogeneity, Personalized therapy  \n*Correspondence:  \nFurong Zeng [zengflorachn@hotmail.com](zengflorachn@hotmail.com)[ ](zengflorachn@hotmail.com)Guangtong Deng [dengguangtong@outlook.com](dengguangtong@outlook.com)  \n1Department of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya road, Changsha, Hunan 410008, China  \n2National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, China  \n3Furong Laboratory, Changsha, Hunan, China  \n4Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China  \n5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China  \n6Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China  \n7Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/.  \nLe et al. Molecular Cancer (2025) 24:22","cbCaiaAuqqj9zGHZ","https://ap.wps.com/l/cbCaiaAuqqj9zGHZ","pdf",4586923,29,"English","# Abstract\n# Introduction\n## Cancer heterogeneity and limitations of bulk sequencing\n## Advances of single-cell multi-dimensional omics\n# Single-cell multi-omics technologies in immunotherapy","[{\"question\":\"What problem does the review focus on in cancer immunotherapy?\",\"answer\":\"It focuses on how cancer’s complexity and tumor heterogeneity limit broad therapeutic efficacy and personalized treatment success.\"},{\"question\":\"What do single-cell multi-omics approaches enable at a high level?\",\"answer\":\"They enable multi-dimensional analyses (genomics, transcriptomics, epigenomics, proteomics, and spatial omics) to dissect tumor heterogeneity at single-cell resolution.\"},{\"question\":\"Which applications does the review highlight for single-cell multi-omics in cancer research?\",\"answer\":\"It emphasizes understanding tumor heterogeneity, immune escape mechanisms, treatment resistance, minimal residual disease monitoring, and neoantigen discovery.\"}]","Single-cell multi-omics in cancer immunotherapy - from tumor heterogeneity to personalized precision treatment | PDF",1790202259,73]