What question did this study set out to answer?

The aim is to explore how natural killer (NK) cells inhibit tumor metastasis and the limitations posed by the tumor microenvironment (TME).

March 12, 2026Open Access

Research Progress on NK Cell Anti-tumor Metastasis

KDKeshan DongChinese Academy of Medical Sciences & Peking Union Medical College YZYang ZhangNanjing University of Science and Technology XDXinke DuTianjin University of Traditional Chinese Medicine

Key Points

The aim is to explore how natural killer (NK) cells inhibit tumor metastasis and the limitations posed by the tumor microenvironment (TME).
Literature review of NK cell functions in tumor metastasis
Analysis of immune suppression in TME
Investigation of interactions between NK cells and other TME components
Evaluation of therapeutic strategies targeting NK cell activation and TME suppression
NK cell number and activity negatively correlate with tumor metastasis
Immunosuppressive cells in TME significantly weaken NK cell functions
Current therapies focusing on enhancing NK cell activity are insufficient due to TME suppression
A dual approach enhancing NK cell activity while overcoming TME suppression is proposed for better treatment outcomes.

Abstract

肿瘤转移的发生高度依赖于免疫抑制性肿瘤微环境（Tumor Microenvironment, TME）。自然杀伤细胞（Natural Killer cell, NK cells）因其非特异性免疫杀伤特性，在肿瘤转移各个阶段均发挥重要的抑制作用。NK细胞数量和功能活性与肿瘤转移呈负相关，且基于NK细胞的免疫治疗在多种转移性肿瘤中已展现出初步疗效。然而，TME中免疫抑制细胞如调节性T细胞（Regulatory T cells，Tregs）、肿瘤相关巨噬细胞（(Tumor-associated Macrophages，TAMs）、髓系来源抑制性细胞（Myeloid-derived Suppressor Cells，MDSCs）、非免疫成分如肿瘤相关成纤维细胞（Cancer-associated Fibroblasts，CAFs）和血小板及代谢障碍等多重因素共同作用，显著削弱NK细胞的浸润和效应功能，限制其抗肿瘤转移能力。目前，大多数针对NK细胞的抗肿瘤治疗策略主要聚焦于其活性的增强，却忽视TME的系统性抑制，导致临床疗效不理想。因此，本文系统综述了NK细胞在肿瘤转移中的抑制作用及其分子机制，深入分析TME如何通过免疫细胞、基质细胞及代谢特征共同限制NK细胞功能，并提出“增强NK细胞活性并解除TME抑制”的双向发力的治疗策略，为NK细胞介导的抗肿瘤转移免疫治疗提供新的理论依据和治疗策略。

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