Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 236-244 http://medscipublisher.com/index.php/cge 242 Future research should integrate multi-omics and spatial analysis methods to conduct more prospective and long-term follow-up studies to gain a more comprehensive understanding of the dynamic changes of TIME during the recurrence process. Meanwhile, it is also necessary to confirm the mechanism of action of specific immune components in recurrence through functional experiments and intervention studies, so as to formulate more appropriate immunotherapy measures and reduce tumor recurrence (Shrestha et al., 2024). 7 Concluding Remarks The continuous changes in the tumor immune microenvironment (TIME) are an important factor in determining whether hepatocellular carcinoma recurs after surgery. Tumors evade the surveillance of the immune system by forming inhibitory TIME, promoting their own growth and spread, while weakening the effect of immunotherapy, thereby increasing the risk of postoperative recurrence for patients. Understanding the dynamic relationship among immune cells, cytokines and tumor cells is of great significance for predicting recurrence and guiding treatment. The core of the new immunotherapy approach lies in paying attention to the changes in the tumor immune microenvironment (TIME) and taking timely measures to reduce recurrence. For instance, the use of immune checkpoint inhibitors to eliminate inhibitory immune cells, as well as the application of novel delivery methods such as hydrogels or nanoparticles, have shown potential to improve TIME, enhance the function of cytotoxic T cells, and alleviate postoperative immunosuppression. Incorporating time-related biomarkers into postoperative monitoring is helpful for early detection of recurrence signs and timely intervention. The focus of future clinical management lies in formulating personalized immunotherapy strategies based on the different immune microenvironments of patients. The development of new technologies such as single-cell sequencing and spatial transcriptomics, as well as new immunomodulatory methods, bring hope for more precise risk assessment, real-time monitoring and personalized combined treatment. This not only ensures safety but also enhances the anti-tumor immune effect. In-depth research on the changing patterns of the tumor immune microenvironment is of great significance for promoting the application of these methods and improving the therapeutic effect of liver cancer patients. Acknowledgments Thanks to Dr. Xuan in this project team for collecting and combing the literature during the study. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Abdelhamed W., and El-Kassas M., 2023., Hepatocellular carcinoma recurrence: predictors and management, Liver Research, 7: 321-332. https://doi.org/10.1016/j.livres.2023.11.004 Agosti E., Panciani P.P., Zeppieri M., De Maria L., Pasqualetti F., Tel A., Zanin L., Fontanella M., and Ius T., 2023, Tumor microenvironment and glioblastoma cell interplay as promoters of therapeutic resistance, Biology, 12(5): 736. https://doi.org/10.3390/biology12050736 Andersen L., Nørgaard M., Rasmussen M., Fredsøe J., Borre M., Ulhøi B., and Sørensen K., 2021, Immune cell analyses of the tumor microenvironment in prostate cancer highlight infiltrating regulatory T cells and macrophages as adverse prognostic factors, The Journal of Pathology, 255(2): 155-165. https://doi.org/10.1002/path.5757 Benmelech S., Le T., McKay M., Nam J., Subramaniam K., Tellez D., Vlasak G., and Mak M., 2024, Biophysical and biochemical aspects of immune cell-tumor microenvironment interactions, APL Bioengineering, 8(2): 021502. https://doi.org/10.1063/5.0195244 Chen C., Wang Z., Ding Y., and Qin Y., 2023, Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma, Frontiers in Immunology, 14: 1133308. https://doi.org/10.3389/fimmu.2023.1133308 Chen J., Qiao Y., Li X., Xu J., Ye Q., Jiang N., Zhang H., and Wu X., 2020, Intratumoral CD45+CD71+erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma, Cancer Letters, 499: 85-98. https://doi.org/10.1016/j.canlet.2020.12.003
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