Research advances in the tumor microenvironment of colorectal cancer liver metastases_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Ercong ¹ , JIANG Lei ² , CHEN Tao ¹ , YAN Junqian ¹ , CHEN Yang ¹ , LI Fang ¹ ,  WANG Jun ²

1. The First Clinical College of Medicine, Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding?author：

WANG Jun, Email: juan_phd@163.com

Keywords：

colorectal cancer; colorectal cancer liver metastasis; tumor microenvironment; molecular targeted therapy

DOI：

10.7507/1007-9424.202506114

Video：

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Objective This study aims to systematically review the dynamic evolution mechanisms of the tumor microenvironment (TME) in colorectal cancer liver metastasis (CRLM), to provide a theoretical basis for developing early diagnostic biomarkers and novel therapeutic targets for CRLM. Methods By integrating the present research, this review focuses on the key multi-step processes involved in CRLM-TME formation. And elaborates the complex interactions among tumor cells, stromal cells, immune components, and key signaling pathways during this process. Results The formation of the CRLM-TME involves several key steps: remote regulation by the primary tumor, specific recruitment of immune cells, adaptive remodeling of the liver microenvironment, and final colonization of the metastatic sites. This process is collectively driven by various factors such as tumor-derived metabolites, specific immune cell subsets, stromal components, and neovascularization, ultimately acts on the entire cascade of cancer cell invasion, migration, and colonization to the liver. Conclusions The CRLM-TME plays a critical role in the development, progression, treatment and drug resistance of CRLM. In-depth exploration of its mechanisms can provide direction for the development of early diagnostic biomarkers and therapies targeting the CRLM-TME, thereby aiming to improve the prognosis of CRLM patients.

Citation： WANG Ercong, JIANG Lei, CHEN Tao, YAN Junqian, CHEN Yang, LI Fang, WANG Jun. Research advances in the tumor microenvironment of colorectal cancer liver metastases. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(1): 104-112. doi: 10.7507/1007-9424.202506114 Copy

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2. 中國醫師協會外科醫師分會, 中華醫學會外科學分會胃腸外科學組, 中華醫學會外科學分會結直腸外科學組, 等. 中國結直腸癌肝轉移診斷和綜合治療指南(2023版). 中國實用外科雜志, 2023, 15(2): 86-99.
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4. Mielgo A, Schmid MC. Liver tropism in cancer: the hepatic metastatic niche. Cold Spring Harb Perspect Med, 2020, 10(3): a037259. doi: 10.1101/cshperspect.a037259.
5. Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell, 2016, 30(5): 668-681.
6. Peinado H, Lavotshkin S, Lyden D. The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol, 2011, 21(2): 139-146.
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12. Liu Y, Zhang X, Gu W, et al. Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: mechanisms and therapeutic prospects. J Adv Res, 2025, 71: 399-413.
13. Watabe T, Takahashi K, Pietras K, et al. Roles of TGF-β signals in tumor microenvironment via regulation of the formation and plasticity of vascular system. Semin Cancer Biol, 2023, 92: 130-138.
14. Hoshino A, Costa-Silva B, Shen TL, et al. Tumour exosome integrins determine organotropic metastasis. Nature, 2015, 527(7578): 329-335.
15. Chen J, Cui L, Lu S, et al. Amino acid metabolism in tumor biology and therapy. Cell Death Dis, 2024, 15(1): 42. doi: 10.1038/s41419-024-06435-w.
16. Zhao S, Mi Y, Guan B, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol, 2020, 13(1): 156. doi: 10.1186/s13045-020-00991-2.
17. Pei W, Wei K, Wu Y, et al. Colorectal cancer tumor cell-derived exosomal miR-203a-3p promotes CRC metastasis by targeting PTEN-induced macrophage polarization. Gene, 2023, 885: 147692. doi: 10.1016/j.gene.2023.147692.
18. Gu Y, Mi Y, Cao Y, et al. The lncRNA MIR181A1HG in extracellular vesicles derived from highly metastatic colorectal cancer cells promotes liver metastasis by remodeling the extracellular matrix and recruiting myeloid-derived suppressor cells. Cell Biosci, 2025, 15(1): 23. doi: 10.1186/s13578-025-01365-2.
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30. Cao X, Lan Q, Xu H, et al. Granulocyte-like myeloid-derived suppressor cells: the culprits of neutrophil extracellular traps formation in the pre-metastatic niche. Int Immunopharmacol, 2024, 143(Pt 3): 113500. doi: 10.1016/j.intimp.2024.113500.
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