《生命科学》 2023, 35(11): 1442-1449

肿瘤微环境可视化技术研究进展

张　娜 , 生安志 , 金海振 , 郭莉莉 , 孙　攀 , 张　含 , 杨晓华 , 田　聆^*

上海交通大学医学院附属胸科医院•上海市胸科医院中心实验室，上海 200025

摘　要：

肿瘤的发生、发展与转移等生物学行为与肿瘤微环境(tumor microenvironment, TME) 密切相关。TME 中的非癌细胞( 如成纤维细胞、免疫细胞、内皮细胞等) 及细胞外基质等对肿瘤细胞的生物学行为有着极其重要的影响；TME 中的生理参数( 如细胞的组成和丰度、关键基因的表达等) 与肿瘤的增殖、侵袭和转移密切相关。免疫治疗是一种很有潜力的肿瘤治疗方法，然而，TME 的异质性可能是导致免疫耐受的原因之一。对TME 的可视化研究，可直观描绘TME 中不同细胞类型的动态行为，在时间与空间维度揭示TME 与肿瘤生长、侵袭的协同关系，发现更多潜在的免疫治疗靶点，提高免疫治疗的有效性。因此，TME 研究模型与可视化技术对于TME 的可视化研究至关重要。本文主要综述了3D 培养系统、类器官与人源化PDX 等TME 可视化研究模型以及多重免疫组织化学、多重免疫荧光、成像型质谱流式和CRISPR/Cas9 基因编辑等技术在TME 可视化研究中的应用进展。

通讯作者：田　聆 , Email:TL09168@hotmail.com

Advances in visualization technologies for tumor microenvironment research

ZHANG Na , SHENG An-Zhi , JIN Hai-Zhen , GUO Li-Li , SUN Pan , ZHANG Han , YANG Xiao-Hua , TIAN Ling^*

Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China

Abstract:

The tumor microenvironment (TME) describes the influence on tumor behavior of non-cancerous cells, including fibroblasts, immune cells,  endothelial cells, inflammatory cells, lymphocytes, etc, and extracellular matrix that support the growth of cancer cells. The physiological parameters of TME, including the composition and abundance of cells and the expression of key genes, are closely related to tumor growth, invasion and metastasis. Immunotherapy is a currently promising approach to tumor treatment. However, the heterogeneity of TME may be one of the reasons for immune tolerance. Visualization of TME can directly depict the dynamic behavior of different cells in TME, reveal the synergistic relationship between TME and tumor growth and invasion in both spatial and temporal dimensions, discover more potential new molecular targets, and improve the effectiveness of immunotherapy. The research models and visualization technologies are very important for the visualization research of TME. Herein, we mainly reviewed the advances in research models, such as 3D culture system, organoids, and humanized PDX research model, etc, as well as the mainstream visualization technologies for TME visualization, such as immunohistochemical techniques, multiple immunofluorescence  techniques, image-type mass spectrometry flow technology, and CRISPR/Cas9 genome editing  technology, etc.

Communication Author：TIAN Ling , Email:TL09168@hotmail.com