PD-1 和 TIGIT 共表达的 CD8+CD103+组织驻留记忆细胞在子宫内膜癌中作为免疫治疗的潜在靶点

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.

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 (T RM ) cells. Additionally, in vitro cell experiments were conducted to assess the functional impact of PD-1 and TIGIT blockade on T-cell activity.

Our analysis identified a significant co-expression of PD-1 and TIGIT in T RM cells within the EC tumor microenvironment. These T RM 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.

T RM 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.