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Functional Subtypes of Macrophages in the Tumor Microenvironment from a Single-Cell Perspective


ZHENG Yuxiao1,2, WANG Hongyan1,2*

(1Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; 2State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China)
Abstract:

The initiation and progression of tumors were closely associated with the tumor microenvironment. TAM (tumor-associated macrophage), serving as key immune cells within this milieu, exhibited significant heterogeneity. This rendered the conventional M1/M2 binary classification inadequate for accurately delineating their functional profiles. Leveraging single-cell RNA sequencing technology, this review refined the classification of TAMs into six distinct subtypes based on functional modules across multiple tumor types, including hepatocellular carcinoma, colorectal cancer, and pancreatic cancer. The subtypes were categorized as follows: pro-angiogenic/tumormetastatic, immunosuppressive, immunostimulatory, proliferative, metabolic, and a minor group of other specialized subtypes. Furthermore, the review provided the marker genes and signature gene sets specific to each TAM subtype and evaluated the translational potential of several key indicators in clinical settings. Considering the limitations and shortcomings inherent in current research, new perspectives were proposed on how single-cell RNA sequencing technology could contribute to advancing precision medicine in oncology.


CSTR: 32200.14.cjcb.2026.02.0021