Shujin Li, Tian Feng, Yuantong Liu, Qichao Yang, An Song, Shuo Wang, Jun Xie, Junjie Zhang, Bifeng Yuan, Zhijun Sun
{"title":"抑制 m1A 可通过下调 MYC/PD-L1 信号促进溶瘤病毒诱导的抗肿瘤免疫力","authors":"Shujin Li, Tian Feng, Yuantong Liu, Qichao Yang, An Song, Shuo Wang, Jun Xie, Junjie Zhang, Bifeng Yuan, Zhijun Sun","doi":"10.1038/s41368-024-00304-0","DOIUrl":null,"url":null,"abstract":"<p><i>N</i><sup>1</sup>-methyladenosine (m<sup>1</sup>A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using <i>Tgfbr1</i> and <i>Pten</i> conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m<sup>1</sup>A modification levels. Analysis of m<sup>1</sup>A-associated genes identified TRMT61A as a key m<sup>1</sup>A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m<sup>1</sup>A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m<sup>1</sup>A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m<sup>1</sup>A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m<sup>1</sup>A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.</p>","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":null,"pages":null},"PeriodicalIF":10.8000,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling\",\"authors\":\"Shujin Li, Tian Feng, Yuantong Liu, Qichao Yang, An Song, Shuo Wang, Jun Xie, Junjie Zhang, Bifeng Yuan, Zhijun Sun\",\"doi\":\"10.1038/s41368-024-00304-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><i>N</i><sup>1</sup>-methyladenosine (m<sup>1</sup>A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using <i>Tgfbr1</i> and <i>Pten</i> conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m<sup>1</sup>A modification levels. Analysis of m<sup>1</sup>A-associated genes identified TRMT61A as a key m<sup>1</sup>A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m<sup>1</sup>A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m<sup>1</sup>A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m<sup>1</sup>A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m<sup>1</sup>A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.</p>\",\"PeriodicalId\":14191,\"journal\":{\"name\":\"International Journal of Oral Science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.8000,\"publicationDate\":\"2024-05-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Oral Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41368-024-00304-0\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Oral Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41368-024-00304-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
N1-methyladenosine (m1A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 and Pten conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels. Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.
期刊介绍:
The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to:
Oral microbiology
Oral and maxillofacial oncology
Cariology
Oral inflammation and infection
Dental stem cells and regenerative medicine
Craniofacial surgery
Dental material
Oral biomechanics
Oral, dental, and maxillofacial genetic and developmental diseases
Craniofacial bone research
Craniofacial-related biomaterials
Temporomandibular joint disorder and osteoarthritis
The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.