肿瘤细胞治疗研究
英文原题：NK cells in breast cancer.
自然杀伤（NK）细胞是固有抗肿瘤免疫的效应细胞，但其在实体瘤中的治疗潜力在很大程度上仍未实现。
自然杀伤（NK）细胞是固有抗肿瘤免疫的效应细胞，但其在实体瘤中的治疗潜力在很大程度上仍未实现。乳腺癌正是这一悖论的例证：NK细胞存在于循环中，也可在肿瘤内检测到，但其细胞毒性活性有限。近期单细胞和空间图谱分析的进展揭示，乳腺癌中NK细胞的功能障碍并非源于单纯的免疫缺失，而是由肿瘤生态系统施加的多层次约束所致。可溶性介质、代谢压力、基质结构和抑制性免疫网络重编程了NK细胞的身份，并使激活与细胞毒性脱偶联。理解这些约束如何塑造NK细胞状态，可将乳腺癌重新定义为固有免疫功能障碍的一种模型，并凸显通过免疫疗法重建NK细胞功能的新机遇。
Natural killer (NK) cells are effectors of innate antitumor immunity, yet their therapeutic potential in solid tumors remains largely unrealized. Breast cancer exemplifies this paradox: NK cells are present in circulation and detectable within tumors, but their cytotoxic activity is limited. Recent advances in single-cell and spatial profiling reveal that NK-cell failure in breast cancer does not result from simple immune absence but from multilayered constraints imposed by the tumor ecosystem. Soluble mediators, metabolic pressures, stromal architecture, and suppressive immune networks reprogram NK-cell identity and uncouple activation from cytotoxicity. Understanding how these constraints shape NK-cell states reframes breast cancer as a model of innate immune dysfunction and highlights new opportunities to reestablish NK-cell function through immunotherapies.
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