Single-cell transcriptomics analysis reveals a disrupted NK-T cell interaction network in liver metastatic cancer
Abstract 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 rol...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-06241-0 |
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| author | Xiaoshuang Wang Zhongen Wu Yan Zhou Dehua Yang Qingtong Zhou Di Zhu Ming-Wei Wang Lu Wang |
| author_facet | Xiaoshuang Wang Zhongen Wu Yan Zhou Dehua Yang Qingtong Zhou Di Zhu Ming-Wei Wang Lu Wang |
| author_sort | Xiaoshuang Wang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-41855cde494841139f19ffbd63f14928 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-41855cde494841139f19ffbd63f149282025-08-20T03:38:15ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-06241-0Single-cell transcriptomics analysis reveals a disrupted NK-T cell interaction network in liver metastatic cancerXiaoshuang Wang0Zhongen Wu1Yan Zhou2Dehua Yang3Qingtong Zhou4Di Zhu5Ming-Wei Wang6Lu Wang7Shanghai Cancer Center, Shanghai Medical College, Fudan UniversitySchool of Pharmacy, Fudan UniversityThe National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of SciencesThe National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of SciencesSchool of Basic Medical Sciences, Fudan UniversitySchool of Pharmacy, Fudan UniversitySchool of Basic Medical Sciences, Fudan UniversityShanghai Cancer Center, Shanghai Medical College, Fudan UniversityAbstract 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.https://doi.org/10.1038/s41598-025-06241-0NK-T interactionLiver metastasisSingle-cell transcriptomics |
| spellingShingle | Xiaoshuang Wang Zhongen Wu Yan Zhou Dehua Yang Qingtong Zhou Di Zhu Ming-Wei Wang Lu Wang Single-cell transcriptomics analysis reveals a disrupted NK-T cell interaction network in liver metastatic cancer Scientific Reports NK-T interaction Liver metastasis Single-cell transcriptomics |
| title | Single-cell transcriptomics analysis reveals a disrupted NK-T cell interaction network in liver metastatic cancer |
| title_full | Single-cell transcriptomics analysis reveals a disrupted NK-T cell interaction network in liver metastatic cancer |
| title_fullStr | Single-cell transcriptomics analysis reveals a disrupted NK-T cell interaction network in liver metastatic cancer |
| title_full_unstemmed | Single-cell transcriptomics analysis reveals a disrupted NK-T cell interaction network in liver metastatic cancer |
| title_short | Single-cell transcriptomics analysis reveals a disrupted NK-T cell interaction network in liver metastatic cancer |
| title_sort | single cell transcriptomics analysis reveals a disrupted nk t cell interaction network in liver metastatic cancer |
| topic | NK-T interaction Liver metastasis Single-cell transcriptomics |
| url | https://doi.org/10.1038/s41598-025-06241-0 |
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