Wang Xiaoshuang, Wu Zhongen, Zhou Yan, Yang Dehua, Zhou Qingtong, Zhu Di, Wang Ming-Wei, Wang Lu
Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
School of Pharmacy, Fudan University, Shanghai, 201203, China.
Sci Rep. 2025 Jul 1;15(1):20576. doi: 10.1038/s41598-025-06241-0.
Natural killer (NK) cells and T cells play crucial roles in liver metastatic cancer, particularly through their cytotoxic effects on tumor cells. Although existing evidence suggests a functional network of mutual regulation between NK and T cells, the nature of their interaction and its role in liver metastasis remain elusive. In this study, we analyzed single-cell transcriptomics of liver metastases and adjacent tissues from nasopharyngeal carcinoma (NPC), thyroid carcinoma (THCA), breast cancer (BC), colorectal cancer (CRC) and cervical cancer (CESC) to uncover the NK-T cell interaction network and its functional implications. In adjacent tissues, we observed increased infiltration of CD8 NKT-like cells, γδT cells, and NK cells. The interaction between CD8 NKT-like cells, CD8 T cells, γδT cells, and NK cells were enhanced, with stronger signals associated with T and NK cell functions. Notably, CD8 NKT-like cells, CD8 T cells, and γδT cells exhibited an increased capacity to activate NK cells. These T cell subsets promoted NK cell anti-tumor activity via CD48-CD244 and TNF-TNFR signaling pathways, which in turn activated the ERK, JNK, and MAPK cascades. Our findings provide valuable insights into the NK-T cell interaction network in liver metastatic cancer, highlighting its potential as a therapeutic target.
自然杀伤（NK）细胞和T细胞在肝转移性癌中发挥着关键作用，特别是通过它们对肿瘤细胞的细胞毒性作用。尽管现有证据表明NK细胞和T细胞之间存在相互调节的功能网络，但其相互作用的本质及其在肝转移中的作用仍不清楚。在本研究中，我们分析了鼻咽癌（NPC）、甲状腺癌（THCA）、乳腺癌（BC）、结直肠癌（CRC）和宫颈癌（CESC）肝转移灶及邻近组织的单细胞转录组学，以揭示NK-T细胞相互作用网络及其功能意义。在邻近组织中，我们观察到CD8 NKT样细胞、γδT细胞和NK细胞的浸润增加。CD8 NKT样细胞、CD8 T细胞、γδT细胞和NK细胞之间的相互作用增强，与T细胞和NK细胞功能相关的信号更强。值得注意的是，CD8 NKT样细胞、CD8 T细胞和γδT细胞激活NK细胞的能力增强。这些T细胞亚群通过CD48-CD244和TNF-TNFR信号通路促进NK细胞的抗肿瘤活性，进而激活ERK、JNK和MAPK级联反应。我们的研究结果为肝转移性癌中的NK-T细胞相互作用网络提供了有价值的见解，突出了其作为治疗靶点的潜力。
