ObjectiveThis 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. MethodsBy 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. ResultsThe 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. ConclusionsThe 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.
Objective To systematically summarize the role of immune cells in the progression of anastomotic leak (AL) following colorectal cancer (CRC) surgery, with an emphasis on the molecular mechanisms of metabolic reprogramming in relevant immune cells, aiming to provide new insights for the diagnosis and treatment of AL. MethodWe reviewed recent literature on the metabolic reprogramming of immune cells in AL following CRC surgery. ResultsIn the postoperative CRC AL microenvironment, homeostasis imbalance drives metabolic reprogramming of immune cells (macrophages, neutrophils), manifested as enhanced glycolysis, impaired fatty acid oxidation, and tricarboxylic acid cycle disruption. Accumulated metabolites (lactate, succinate), along with acidic pH, hypoxia, and immune factors, collectively shape an intertwined immunosuppressive and pro-inflammatory microenvironment that impedes anastomotic healing. Targeting key nodes in this metabolic reprogramming offers potential therapeutic strategies and a theoretical framework for clinical translation in AL. ConclusionsImmune cells, as key components of the AL microenvironment, play an important role in the initiation and progression of AL. In-depth exploration of the molecular mechanisms underlying metabolic reprogramming of relevant immune cells may provide directions for the diagnosis and treatment of AL, with the aim of improving patients’ outcomes.
ObjectiveTo summarize the key roles of M2-tumor-associated macrophages (M2-TAMs) in the progression of colorectal cancer (CRC) through the regulation of signaling pathways, and to discuss corresponding potential intervention strategies. MethodBased on a systematic review of published literature, this article comprehensively analyzes the key roles of M2-TAMs in the signaling pathways governing CRC progression and summarizes the upstream pathways regulating M2-TAMs recruitment and polarization, as well as the core downstream effector networks driving their pro-tumorigenic functions. ResultsAmong the upstream pathways of M2-TAMs, cytokine/chemokine pathways (CCL2/CCR2, CSF-1R, IL-6/JAK/STAT3, and CXCL12-CXCR4) mediate chemotactic recruitment and pro-tumor polarization, whereas metabolic sensing pathways (lactate and succinate) shape the pro-tumor phenotype of TAMs through metabolic reprogramming. The downstream effector pathways exhibit a clear functional division: the EGF/EGFR/PI3K/Akt/mTOR axis primarily mediates proliferation and survival, whereas the TGF-β/Smad/non-Smad, Wnt/β-catenin, and Notch/Jagged1 pathways synergistically drive invasion and metastasis. These pathways coordinately facilitate the pro-tumorigenic effects of M2-TAMs. Based on the above mechanisms, intervention strategies targeting key nodes such as CSF-1R, CCR2, and CXCR4 provide promising therapeutic options for CRC. ConclusionsThis review elucidates the key regulatory roles of M2-TAMs in CRC signaling networks. Based on these findings, multi-pathway combinatorial blockade and precise modulation of TAMs subpopulations deserve further investigation. However, TAMs plasticity, signal context-dependency, and microenvironment heterogeneity remain core bottlenecks limiting clinical translation. Future efforts should focus on the development of novel therapeutic modalities and the design and validation of combination regimens to promote the clinical translation of TAMs-targeted therapeutic strategies.