| 摘要: |
| ［摘要］ 肿瘤免疫治疗的临床获益显著受限于肿瘤微环境的高度空间异质性，尤其是免疫“冷区”的存在。空间转录组学技术的突破，使得在亚细胞及单细胞分辨率下解析免疫逃逸的空间拓扑构架成为可能。该文系统阐述空间转录组学在识别“荒漠型”与“排斥型”生态位中的应用，探讨三级淋巴结构的成熟度梯度及其空间分布在决定效应细胞浸润效率中的核心作用。基于此，该文提出剖析肿瘤免疫微环境应从单纯的“空间描述”向“功能性空间干预”模式转变。通过重塑表观遗传、精准阻断代谢通路及诱导高内皮静脉生成，重构免疫允许性微环境，为克服实体瘤免疫治疗抵抗提供基于空间生物学的科学理论依据。 |
| 关键词: 空间转录组学 肿瘤微环境 三级淋巴结构 免疫“冷区” 功能性空间干预 免疫治疗耐受 |
| DOI：10.3969/j.issn.1674-3806.2026.05.22 |
| 分类号:R 730 |
| 基金项目:广西自然科学基金项目（编号：2023GXNSFAA026033）；国家自然科学基金项目（编号：82560501，82073004） |
|
| Spatial transcriptomics-driven strategies for decoding and functional remodeling of tumor “immune cold zones” |
|
QU Ziquan1, CHEN Qicong2, WEI Jiazhang3
|
|
1.School of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; 2.Institute of Tumor Research, Guangxi Academy of Medical Sciences, Nanning 530021, China; 3.Department of Otolaryngology-Head and Neck, the People′s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China
|
| Abstract: |
| ［Abstract］ The clinical benefits of tumor immunotherapy are significantly limited by the profound spatial heterogeneity of the tumor microenvironment, especially the existence of “immune cold zones”. The breakthrough of spatial transcriptomics(ST) technology has made it possible to empower high-resolution dissection of the spatial topological framework of immune evasion at subcellular and single-cell scales. This paper systematically describes the application of ST in identifying immune-desert and immune-excluded niches, and discusses the core role of tertiary lymphoid structures maturity-related gradients and their spatial distribution in determining the efficiency of effector cell infiltration. On this basis, this paper proposes that the dissection of the tumor immune microenvironment should transition from simple “spatial description” to a “functional spatial intervention” model. By remodeling epigenetics, precisely blocking metabolic pathways, and inducing the generation of high endothelial venules, the immunopermissive microenvironment can be reconstructed, providing a scientific theoretical basis based on spatial biology for overcoming immunotherapy resistance in solid tumors. |
| Key words: Spatial transcriptomics(ST) Tumor microenvironment Tertiary lymphoid structures Immune cold zones Functional spatial intervention Immunotherapy resistance |
