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Chemotherapy-induced high expression of IL23A enhances efficacy of anti-PD-1 therapy in TNBC by co-activating the PI3K-AKT signaling pathway of CTLs.
Pan, Fan; Liu, Jiajing; Chen, Ying; Zhu, Binghan; Chen, Weiwei; Yang, Yuchen; Zhu, Chunyan; Zhao, Hua; Liu, Xiaobei; Xu, Yichen; Xu, Xiaofan; Huo, Liqun; Xie, Li; Wang, Rui; Gu, Jun; Huang, Guichun.
Afiliación
  • Pan F; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Liu J; Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Ningbo University, Liuting Road 59#, Ningbo, 315010, China.
  • Chen Y; Medical School of Nanjing University, Nanjing University, Hankou Road 22#, Nanjing, 210093, China.
  • Zhu B; Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing University Medical School, Zhongshan Road 321#, Nanjing, 210008, China.
  • Chen W; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Yang Y; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Zhu C; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Zhao H; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Liu X; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Xu Y; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Xu X; Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Huo L; Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China.
  • Xie L; Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321#, Nanjing, 210008, China. xieli@njglyy.com.
  • Wang R; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China. wangrui218@163.com.
  • Gu J; Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China. gujunjiangsu@outlook.com.
  • Huang G; Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Eastern Zhongshan Road 305#, Nanjing, 210002, China. huangguichun@nju.edu.cn.
Sci Rep ; 14(1): 14248, 2024 06 20.
Article en En | MEDLINE | ID: mdl-38902343
ABSTRACT
Treatment of advanced triple-negative breast cancer (TNBC) is a great challenge in clinical practice. The immune checkpoints are a category of immunosuppressive molecules that cancer could hijack and impede anti-tumor immunity. Targeting immune checkpoints, such as anti-programmed cell death 1 (PD-1) therapy, is a promising therapeutic strategy in TNBC. The efficacy and safety of PD-1 monoclonal antibody (mAb) with chemotherapy have been validated in TNBC patients. However, the precise mechanisms underlying the synergistic effect of chemotherapy and anti-PD-1 therapy have not been elucidated, causing the TNBC patients that might benefit from this combination regimen not to be well selected. In the present work, we found that IL-23, an immunological cytokine, is significantly upregulated after chemotherapy in TNBC cells and plays a vital role in enhancing the anti-tumor immune response of cytotoxic T cells (CTLs), especially in combination with PD-1 mAb. In addition, the combination of IL-23 and PD-1 mAb could synergistically inhibit the expression of Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), which is a regulatory subunit of PI3K and inhibit p110 activity, and promote phosphorylation of AKT in TNBC-specific CTLs. Our findings might provide a molecular marker that could be used to predict the effects of combination chemotherapy therapy and PD-1 mAb in TNBC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Transducción de Señal / Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt / Subunidad p19 de la Interleucina-23 / Receptor de Muerte Celular Programada 1 / Neoplasias de la Mama Triple Negativas Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Transducción de Señal / Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt / Subunidad p19 de la Interleucina-23 / Receptor de Muerte Celular Programada 1 / Neoplasias de la Mama Triple Negativas Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido