[Research Advances on the Immune Evasion Mechanisms of Disseminated Tumor Cells and Their Roles in Cancer Metastasis] – Research

Tumor metastasis is the leading cause of cancer-related mortality. Disseminated tumor cells (DTCs), serving as the critical ‘seeds’ in the metastatic cascade, hold the key to determining the success or failure of metastasis. Following dissemination from the primary tumor and colonization of distant organs, DTCs often enter a prolonged state of dormancy. Their subsequent escape from immune surveillance through sophisticated mechanisms enables them to transition from this dormant state to a proliferative one, ultimately culminating in clinically detectable metastatic lesions. A profound understanding of DTCs immune evasion is therefore essential for unraveling the fundamental biology of metastasis and developing effective anti-metastatic strategies. This article systematically reviewed the latest advances in the mechanisms underlying DTCs immune evasion, focusing on three core aspects: defects in antigen presentation, formation of an immunosuppressive microenvironment, and metabolism reprogramming-mediated immunosuppression. Specifically, DTCs achieve ‘immune invisibility’ by downregulating major histocompatibility complex class-I (MHC-I) molecule expression; they actively construct a local ‘protective shield’ by recruiting immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs); and they impair effector immune cell function at the energetic and metabolic levels by remodeling glucose, amino acid, and lipid metabolism. Building upon this, we innovatively integrate the traditional Chinese medicine (TCM) theories of ‘hidden toxicity due to vital qi deficiency’ and the ‘metastatic state’ to elucidate the dynamic pathogenic relationship between the body’s systemic ‘Zhengqi’ (vital energy) status and the dormancy-awakening switch of DTCs, offering a novel holistic perspective for comprehending the metastatic process. Finally, we discussed the prospects of multi-target combination therapeutic strategies against DTCs immune evasion and highlight the potential of emerging technologies, such as single-cell sequencing and spatial transcriptomics, aiming to provide valuable insights for future in-depth research and clinical translation in the field of anti-metastasis therapy. .

【中文题目：播散肿瘤细胞免疫逃逸机制 及其在肿瘤转移中的作用研究进展】 【中文摘要：肿瘤转移是导致癌症患者死亡的首要原因，而播散肿瘤细胞（disseminated tumor cells, DTCs）作为转移级联反应中的关键“种子”，其命运直接决定了转移的成败。DTCs从原发灶脱落并定殖于远处靶器官后，常进入一种长期休眠状态，随后通过复杂的免疫逃逸机制突破免疫监视，从休眠态激活为增殖态，最终形成临床可评估的转移灶。深入理解DTCs的免疫逃逸机制对于揭示肿瘤转移的本质和开发有效的抗转移策略至关重要。本文系统综述了DTCs免疫逃逸机制的最新研究进展，重点围绕三大核心机制展开：抗原呈递缺陷、免疫抑制微环境的形成以及代谢重编程介导的免疫抑制。具体而言，DTCs通过下调主要组织相容性复合体I类（major histocompatibility complex class-I, MHC-I）分子表达实现“免疫隐身”；主动招募调节性T细胞（regulatory T cells, Tregs）、髓源性抑制细胞（myeloid-derived suppressor cells, MDSCs）等免疫抑制性细胞，构建局部“防护盾”；并通过重塑糖、氨基酸及脂质代谢，从能量与物质层面削弱效应免疫细胞功能。在此基础上，本文创新性地结合中医“正虚伏毒”与“转移态”理论，阐释机体正气盛衰与DTCs休眠-觉醒转换之间的动态病机关系，为从整体调控角度认识转移过程提供了新视角。最后，文章展望了针对DTCs免疫逃逸的多靶点联合治疗策略，以及单细胞测序、空间转录组等新技术在该领域的应用前景，以期为未来抗转移研究的深入与临床转化提供重要参考。 】 【中文关键词：肿瘤转移；播散肿瘤细胞；免疫逃逸；正虚伏毒；转移态】.