Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 236-244 http://medscipublisher.com/index.php/cge 238 various immune cells such as T cells, natural killer (NK) cells, macrophages, dendritic cells and myeloid-derived suppressor cells, as well as non-immune stromal cells such as fibroblasts, endothelial cells and peripheral cells. These cells interact with tumor cells to jointly shape the local immune status, thereby influencing tumor development, immune surveillance and treatment response (Figure 1) (De Visser and Joyce, 2023; Benmelech et al., 2024). Figure 1 Microenvironmental regulation of primary tumor progression and metastasis (Adopted from De Visser and Joyce, 2023) In addition to cellular components, TIME is also regulated by some soluble molecules, including cytokines, chemokines, growth factors and metabolites. These molecules transmit signals between cells to regulate the movement, activation, differentiation or inhibition of immune cells (Chen et al., 2023). In this network, the balance between pro-inflammatory signals and inhibitory signals is very crucial, which determines whether TIME promotes the anti-tumor immune response or helps immune escape and tumor progression (Yu et al., 2025). 3.2 Trends in the immune microenvironment before and after surgery Before surgery, TIME is often subject to the combined effect of multiple factors, which can both promote and inhibit immune responses. In the early stage of a tumor, the microenvironment may be in an inflammatory state, accompanied by active immune surveillance and infiltration of cytotoxic cells. However, as the tumor progresses, TIME usually turns to immunosuppression, manifested as an increase in regulatory T cells, M2-type macrophages and myelium-derived suppressor cells, accompanied by metabolic disorders and hypoxia (Jia et al., 2022; De Visser and Joyce, 2023). After the tumor is surgically removed, the immune microenvironment will further change. Tumor resection may weaken immunosuppression in the short term and restore the immune system to some extent, but the remaining tumor cells or micrometastases may still take the opportunity to evade immune attack. Therefore, in the postoperative stage, there are both opportunities for immune control of the tumor and the risk of immune escape. The specific outcome depends on the overall balance of the immune cell population and cytokine environment (Yeo et al., 2022; Yu et al., 2025). 3.3 Immune Remodeling after tumor resection and immune escape before recurrence After tumor resection, the tumor immune microenvironment (TIME) will continue to change, such as adjustments in the types, quantities and functions of immune cells. At this stage, effector T cells and NK cells may increase, and the secretion of cytokines and chemokines will also be different. These changes can sometimes enhance the immune effect against tumors, and sometimes make immunosuppression more severe. This immune change process is influenced by multiple factors such as surgical injury, remaining tumors, and the patient's original immune status (Yu et al., 2025).
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