PVT1 inhibition stimulates anti-tumor immunity, prevents metastasis, and depletes cancer stem cells in squamous cell carcinoma

• Published in: Cell death & disease Vol. 14; no. 3; p. 187
• Main Authors: Qin, Zhen, Zhang, Wenbo, Liu, Shuo, Wang, Yujia, Peng, Xin, Jia, Lingfei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.03.2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/31; 13/51; 38/91; 45/77; 631/250/2161; 631/67/1536; 64/60; Antibodies; Biochemistry; Biomedical and Life Sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; CD8 antigen; CD8-Positive T-Lymphocytes - pathology; Cell Biology; Cell Culture; Cell Line, Tumor; Cell Proliferation; Chemokines; DNA damage; Gene Expression Regulation, Neoplastic; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - genetics; Humans; Immune checkpoint inhibitors; Immunology; Immunotherapy; Life Sciences; Lymph nodes; Lymphocytes T; Metastases; MicroRNAs - genetics; Molecular modelling; Neoplastic Stem Cells - pathology; PD-1 protein; RNA, Long Noncoding - genetics; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; Stem cells; Tumor Microenvironment; Yes-associated protein
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-023-05710-6

Cancer stem cells (CSCs) cause tumor metastasis and immune evasion by as-yet-unknown molecular mechanisms. In the present study, we identify a long noncoding RNA (lncRNA), termed PVT1 , which is highly expressed in CSCs and correlated closely with lymph node metastasis of head and neck squamous cell carcinoma (HNSCC). PVT1 inhibition eliminates CSCs, prevents metastasis, and stimulates anti-tumor immunity, while inhibiting HNSCC growth. Moreover, PVT1 inhibition promotes the infiltration of CD8 + T cells into the tumor microenvironment, thereby enhancing immunotherapy by PD1 blockade. Mechanistically, PVT1 inhibition stimulates the DNA damage response, which induces CD8 + T cell-recruiting chemokines, while preventing CSCs and metastasis via regulating the miR-375/YAP1 axis. In conclusion, targeting PVT1 might potentiate the elimination of CSCs via immune checkpoint blockade, prevent metastasis, and inhibit HNSCC growth.