Characterization and prognostic of CD8 + TIM3 + CD101 + T cells in glioblastoma multiforme.

in Cell & bioscience by Hong-Liang Wang, Sai Li, Chun-Chun Ma, Xiang-Hu Zheng, Hao-Yuan Wu, Chen-Xi Chang, Zhi-Hao Yang, Jia-Wei Wang, Fa-Ming Pan, Bing Zhao

TLDR

  • The study identified distinct cell types in glioblastoma multiforme (GBM), including CD8+TIM3+CD101+T cells (CCT cells), and developed a prognostic model to predict patient outcomes.
  • The findings suggest potential therapeutic strategies for high-risk patients and provide insights into GBM's immune evasion mechanisms.

Abstract

Glioblastoma multiforme (GBM) is a pervasive and aggressive malignant brain tumor. In the tumor immune microenvironment, CD8 + TIM3 + CD101 + T cells (CCT cells) play a pivotal role in tumor progression and immune evasion. This study aimed to characterize differentially expressed genes (DEGs) in CCT cells, establish a prognostic model for GBM, and explore clinical implications. Analysis of data from TCGA, CGGA, and GEO databases included whole-genome expression profiles, clinical data, single nucleotide mutations, and single-cell RNA sequencing. DEGs were identified, and cell trajectories were constructed using Seurat, Monocle 2, and CellChat packages. Functional enrichment analysis was conducted with clusterProfiler, and a prognostic model was developed. Immune infiltration and drug sensitivity analyses were performed to evaluate therapeutic implications. Eight distinct cell types were distinguished, encompassing T cells, macrophages, neurons, mural cells, endothelial cells, oligodendrocytes, fibroblasts, and B cells. Comparative analysis revealed differences in these cell types between GBM samples with new adjuvant therapy and initial diagnosis controls. Pseudotime analysis indicated CD8 + TIM3 + CD101-T cells as precursors to CCT cells, unveiling unique gene expression patterns during this transition. The prognostic model, incorporating 22 gene features via LASSO regression, demonstrated strong predictive ability through Receiver Operating Characteristic (ROC) curves. Analysis of 28 immune cell types revealed differences between high-risk and low-risk groups, providing insights into GBM's immune evasion mechanisms. Drug sensitivity analysis proposed potential therapeutic strategies for high-risk patients. This study offers an in-depth understanding of CCT cells in GBM, introducing a novel prognostic model and suggesting promising therapeutic approaches.

Overview

  • The study aimed to characterize differentially expressed genes (DEGs) in CD8+TIM3+CD101+T cells (CCT cells) in glioblastoma multiforme (GBM), establish a prognostic model, and explore clinical implications.
  • The study analyzed data from three databases (TCGA, CGGA, and GEO) including whole-genome expression profiles, clinical data, single nucleotide mutations, and single-cell RNA sequencing.
  • The primary objective is to understand the role of CCT cells in GBM and develop a prognostic model to predict patient outcomes and identify potential therapeutic strategies.

Comparative Analysis & Findings

  • The study identified eight distinct cell types in GBM, including T cells, macrophages, neurons, and others, and found differences between GBM samples with new adjuvant therapy and initial diagnosis controls.
  • Pseudotime analysis revealed that CD8+TIM3+CD101-T cells are precursors to CCT cells, with unique gene expression patterns during this transition.
  • The prognostic model incorporating 22 gene features demonstrated strong predictive ability through Receiver Operating Characteristic (ROC) curves, and analysis of 28 immune cell types revealed differences between high-risk and low-risk groups.

Implications and Future Directions

  • The study's findings suggest potential therapeutic strategies for high-risk patients and provide insights into GBM's immune evasion mechanisms.
  • Future studies should aim to validate the prognostic model in larger cohorts and explore the potential of CCT cells as a therapeutic target.
  • Additionally, investigating the role of CCT cells in other types of cancer and exploring novel approaches for targeting immune evasion mechanisms could lead to new therapeutic strategies.
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