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YTHDF2 in peritumoral hepatocytes mediates chemotherapy-induced antitumor immune responses through CX3CL1-mediated CD8+ T cell recruitment.
Yang, Zhenyun; Wang, Xin; Fu, Yizhen; Wu, Weijie; Hu, Zili; Lin, Qingyang; Peng, Wei; Pan, Yangxun; Wang, Juncheng; Chen, Jinbin; Hu, Dandan; Zhou, Zhongguo; Xu, Li; Zhang, Yaojun; Hou, Jiajie; Chen, Minshan.
Afiliação
  • Yang Z; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Wang X; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Fu Y; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • Wu W; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Hu Z; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Lin Q; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • Peng W; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Pan Y; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Wang J; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • Chen J; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Hu D; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Zhou Z; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • Xu L; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Zhang Y; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
  • Hou J; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • Chen M; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.
Mol Cancer ; 23(1): 186, 2024 Sep 06.
Article em En | MEDLINE | ID: mdl-39237909
ABSTRACT
Peritumoral hepatocytes are critical components of the liver cancer microenvironment, However, the role of peritumoral hepatocytes in the local tumor immune interface and the underlying molecular mechanisms have not been elucidated. YTHDF2, an RNA N6-methyladenosine (m6A) reader, is critical for liver tumor progression. The function and regulatory roles of YTHDF2 in peritumoral hepatocytes are unknown. This study demonstrated that oxaliplatin (OXA) upregulated m6A modification and YTHDF2 expression in hepatocytes. Studies using tumor-bearing liver-specific Ythdf2 knockout mice revealed that hepatocyte YTHDF2 suppresses liver tumor growth through CD8+ T cell recruitment and activation. Additionally, YTHDF2 mediated the response to immunotherapy. Mechanistically, OXA upregulated YTHDF2 expression by activating the cGAS-STING signaling pathway and consequently enhanced the therapeutic outcomes of immunotherapeutic interventions. Ythdf2 stabilized Cx3cl1 transcripts in an m6A-dependent manner, regulating the interplay between CD8+ T cells and the progression of liver malignancies. Thus, this study elucidated the novel role of hepatocyte YTHDF2, which promotes therapy-induced antitumor immune responses in the liver. The findings of this study provide valuable insights into the mechanism underlying the therapeutic benefits of targeting YTHDF2.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Ligação a RNA / Linfócitos T CD8-Positivos / Hepatócitos / Quimiocina CX3CL1 / Oxaliplatina / Neoplasias Hepáticas Limite: Animals / Humans Idioma: En Revista: Mol Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de publicação: Reino Unido
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Ligação a RNA / Linfócitos T CD8-Positivos / Hepatócitos / Quimiocina CX3CL1 / Oxaliplatina / Neoplasias Hepáticas Limite: Animals / Humans Idioma: En Revista: Mol Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de publicação: Reino Unido