肿瘤细胞治疗研究
英文原题：Immunotherapy-mediated cancer reversion: Possibilities and prospects.
Immunotherapy-mediated cancer reversion: Possibilities and prospects.
免疫治疗通过免疫激活实现持久的肿瘤控制，彻底改变了癌症治疗。
免疫治疗通过免疫激活实现持久的肿瘤控制，彻底改变了癌症治疗。新出现的证据表明，除了细胞毒性清除之外，免疫反应还可以将恶性细胞重编程为正常化、分化的状态，这一现象被称为免疫治疗介导的癌症逆转。这一范式转变将免疫系统定位为一种修复性力量，而非仅仅是破坏性力量。本综述综合了关于免疫治疗介导的癌症逆转的当代证据，评估了多种恶性肿瘤中的机制通路和临床意义，以建立免疫驱动的表型正常化的概念框架。我们进行了一项全面的叙述性综述，检索了 PubMed、Web of Science 和 Scopus 数据库，涵盖 2015 年至 2025 年的文献。证据按免疫检查点阻断、过继细胞疗法、细胞因子调节和微环境重塑等主题进行综合。免疫介导的逆转通过协调的表观遗传、代谢和微环境重编程而产生。检查点抑制剂通过 IFN 驱动的染色质重塑恢复分化程序，而 CAR-T 和 NK 细胞疗法诱导代谢正常化和上皮修复。细胞因子信号传导和巨噬细胞重编程通过调节血管生成和基质结构来强化逆转。黑色素瘤、肺癌、乳腺癌、血液系统恶性肿瘤和肝细胞癌的临床观察支持这一修复性免疫过程。单细胞和空间组学识别了连接恶性与正常状态的过渡状态。免疫治疗介导的癌症逆转代表了一个概念前沿，将肿瘤学从根除转向修复。未来的进展需要定义生物标志物、确认机制持久性，并重新设计临床终点。随着整合免疫-表观遗传框架的成熟，免疫驱动的逆转可能从生物学奇观演变为通往持久缓解和功能性治愈的临床可重复路径。
Immunotherapy has revolutionized cancer treatment by enabling durable tumor control through immune activation. Emerging evidence suggests that beyond cytotoxic elimination, immune responses can reprogram malignant cells toward normalized, differentiated states, a phenomenon termed immunotherapy-mediated cancer reversion. This paradigm shift positions the immune system as a restorative rather than solely destructive force. This review synthesizes contemporary evidence on immunotherapy-mediated cancer reversion, evaluating mechanistic pathways and clinical implications across diverse malignancies to establish a conceptual framework for immune-driven phenotypic normalization. A comprehensive narrative review was conducted across PubMed, Web of Science, and Scopus databases, encompassing literature from 2015 to 2025. Evidence was synthesized thematically across immune checkpoint blockade, adoptive cell therapies, cytokine modulation, and microenvironmental remodeling. Immune-mediated reversion arises through coordinated epigenetic, metabolic, and microenvironmental reprogramming. Checkpoint inhibitors restore differentiation programs via IFN -driven chromatin remodeling, while CAR-T and NK-cell therapies induce metabolic normalization and epithelial restoration. Cytokine signaling and macrophage reprogramming reinforce reversion by modulating angiogenesis and stromal architecture. Clinical observations across melanoma, lung cancer, breast cancer, hematologic malignancies, and hepatocellular carcinoma support this restorative immune process. Single-cell and spatial omics identify transitional states bridging malignancy and normalcy. Immunotherapy-mediated cancer reversion represents a conceptual frontier shifting oncology from eradication to restoration. Future progress requires defining biomarkers, confirming mechanistic permanence, and redesigning clinical endpoints. As integrative immuno-epigenetic frameworks mature, immune-driven reversion may evolve from biological curiosity to clinically reproducible pathway toward durable remission and functional cure.
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