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PD-1 and TIGIT coexpressing CD8 + CD103 + tissue-resident memory cells in endometrial cancer as potential targets for immunotherapy.
Jiang, Fang; Mao, Mingyi; Jiang, Shiyang; Jiao, Yuhao; Cao, Dongyan; Xiang, Yang.
Afiliación
  • Jiang F; Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynaecologic Diseases, Beijing, China.
  • Mao M; Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynaecologic Diseases, Beijing, China.
  • Jiang S; Ovarian Cancer Program, Department of Gynaecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Jiao Y; Department of Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
  • Cao D; Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynaecologic Diseases, Beijing, China.
  • Xiang Y; Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynaecologic Diseases, Beijing, China. Electronic address: xiangy@pumch.cn.
Int Immunopharmacol ; 127: 111381, 2024 Jan 25.
Article en En | MEDLINE | ID: mdl-38150880
ABSTRACT

BACKGROUND:

Immunotherapy has shown promise in treating various cancers; however, its efficacy in endometrial cancer (EC) remains suboptimal owing to the complex dynamics of the tumour immune microenvironment. This study focuses on exploring the potential of targeting the programmed cell death protein 1 gene (PD-1) and the T cell Immunoreceptor with Ig and ITIM domains gene (TIGIT) coexpressing tissue-resident memory cells in EC.

METHODS:

A comprehensive approach, utilizing RNA sequencing, single-cell RNA sequencing, mass cytometry, and flow cytometry, was employed to analyse the expression patterns of PD-1 and TIGIT in the EC tumor environment and to characterize the phenotypic properties of tumor-infiltrating lymphocytes (TILs), particularly tissue-resident memory (TRM) cells. Additionally, in vitro cell experiments were conducted to assess the functional impact of PD-1 and TIGIT blockade on T-cell activity.

RESULTS:

Our analysis identified a significant co-expression of PD-1 and TIGIT in TRM cells within the EC tumor microenvironment. These TRM cells displayed an exhausted phenotype with impaired cytotoxicity, enhanced proliferative capacity, and diminished cytotoxic activity. In vitro T-cell assays showed that a dual blockade of PD-1 and TIGIT more effectively restored T-cell functionality compared to single blockade, suggesting enhanced therapeutic potential.

CONCLUSIONS:

TRM cells co-expressing PD-1 and TIGIT represent potential targets for EC immunotherapy. Dual immune checkpoint blockade targeting PD-1 and TIGIT may offer an effective therapeutic strategy for EC, providing valuable insights for the development of immunotherapeutic approaches.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Receptor de Muerte Celular Programada 1 Límite: Female / Humans Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Receptor de Muerte Celular Programada 1 Límite: Female / Humans Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos