Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 234-253 http://medscipublisher.com/index.php/cge 236 Chemokines such as CXCL12 play roles in recruiting immune cells to the tumor site and can contribute to either tumor suppression or promotion depending on the context (Lazarus et al., 2018; Zeng et al., 2021). 2.3.3 Extracellular matrix The extracellular matrix (ECM) provides structural support to the tumor and is composed of proteins such as collagen, fibronectin, and laminin. The ECM not only serves as a scaffold for tumor cells but also influences cellular behavior through biochemical and mechanical signals. ECM remodeling, driven by enzymes such as matrix metalloproteinases (MMPs), can facilitate tumor invasion and metastasis. Additionally, the ECM can modulate immune cell function and contribute to the establishment of an immunosuppressive microenvironment (Karlsson and Nyström, 2022; Schmitt and Greten, 2021). 3 Immune Evasion Mechanisms in Colon Cancer Complex immune escape mechanisms are important cause of colon cancer progression (Figure 1). Clarification of these mechanisms is expected to propose new guidance or direction for tumor prevention and control. Figure 1 Immune Evasion Mechanisms in Colon Cancer The immune evasion mechanisms showed in detail, including immune checkpoints, tumor antigen presentation, Fas-FasL pathways and immunosuppressive cells. Bottom: Immune checkpoint inhibitors, including PD-1/PD-L1, CTLA4/CD80 or CD86 restrained T cell activation and function. Left: Inhibit DC maturation and function, decrease HLA-I expression to inhibit tumor antigen presentation. Top: Tregs secrete a variety of cytokines to inhibit the activation and proliferation of T cells; M2 TAMs inhibit the activity of T cells by secreting immunosuppressive cytokines such as IL-10 and TGF-β; MDSCs can promote tumor immune escape by inhibiting the proliferation and activation of T cells; MDSCs polarized to M2 TAMs. Right: FAS/FASL pathway help tumor cells inhibit apoptosis and cause T cell death. 3.1 Immune escape of tumor cells 3.1.1 Immune checkpoints and inhibitory signals Immune checkpoints are crucial modulators of the immune response, ensuring self-tolerance and preventing autoimmunity. However, tumors exploit these pathways to evade immune detection. In colon cancer, immune checkpoints such as PD-1, PD-L1, and CTLA-4 are often upregulated, leading to immune suppression and tumor
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