Sabit Hussein, Arneth Borros, Pawlik Timothy M, Abdel-Ghany Shaimaa, Ghazy Aysha, Abdelazeem Rawan M, Alqosaibi Amany, Al-Dhuayan Ibtesam S, Almulhim Jawaher, Alrabiah Noof A, Hashash Ahmed
Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 3237101, Egypt.
Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Philipps University Marburg, Baldingerstr. 1, 35043 Marburg, Germany.
Pharmaceuticals (Basel). 2025 Jan 10;18(1):75. doi: 10.3390/ph18010075.
Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contributes to cancer progression and therapeutic resistance. These technologies are able to integrate data from molecular genomic, transcriptomic, proteomics, and metabolomics studies of cells at a single-cell resolution scale that give rise to the full cellular and molecular complexity in the TME. Understanding the complex and sometimes reciprocal relationships among cancer cells, CAFs, immune cells, and ECs has led to novel insights into their immense heterogeneity in functions, which can have important consequences on tumor behavior. In-depth studies have uncovered immune evasion mechanisms, including the exhaustion of T cells and metabolic reprogramming in response to hypoxia from cancer cells. Single-cell multi-omics also revealed resistance mechanisms, such as stromal cell-secreted factors and physical barriers in the extracellular matrix. Future studies examining specific metabolic pathways and targeting approaches to reduce the heterogeneity in the TME will likely lead to better outcomes with immunotherapies, drug delivery, etc., for cancer treatments. Future studies will incorporate multi-omics data, spatial relationships in tumor micro-environments, and their translation into personalized cancer therapies. This review emphasizes how single-cell multi-omics can provide insights into the cellular and molecular heterogeneity of the TME, revealing immune evasion mechanisms, metabolic reprogramming, and stromal cell influences. These insights aim to guide the development of personalized and targeted cancer therapies, highlighting the role of TME diversity in shaping tumor behavior and treatment outcomes.
单细胞多组学技术的最新进展使人们有能力识别多种细胞类型并破译肿瘤微环境（TME）的关键组成部分，从而在更深入了解肿瘤微环境异质性如何促进癌症进展和治疗抗性方面取得了重要进展。这些技术能够在单细胞分辨率尺度上整合来自细胞分子基因组学、转录组学、蛋白质组学和代谢组学研究的数据，从而呈现出TME中完整的细胞和分子复杂性。了解癌细胞、癌症相关成纤维细胞（CAFs）、免疫细胞和内皮细胞（ECs）之间复杂且有时相互的关系，为深入了解它们在功能上的巨大异质性提供了新见解，而这种异质性可能对肿瘤行为产生重要影响。深入研究揭示了免疫逃逸机制，包括T细胞耗竭以及癌细胞对缺氧的代谢重编程。单细胞多组学还揭示了耐药机制，如基质细胞分泌因子和细胞外基质中的物理屏障。未来研究特定代谢途径并采用靶向方法以减少TME中的异质性，可能会在免疫疗法、药物递送等癌症治疗方面带来更好的效果。未来的研究将纳入多组学数据、肿瘤微环境中的空间关系，并将其转化为个性化癌症治疗方法。本综述强调了单细胞多组学如何能够洞察TME的细胞和分子异质性，揭示免疫逃逸机制、代谢重编程和基质细胞的影响。这些见解旨在指导个性化和靶向癌症治疗的发展，突出TME多样性在塑造肿瘤行为和治疗结果中的作用。
