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Updated: Jul 1, 2025
Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Bulk anda single-cell transcriptome profiling reveals the molecular characteristics of T cell-mediated tumor killing
Yin-Wei Dai1, Ya-Ting Pan2, Dan-Feng Lin1
1Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Background:
Despite the potential of immune checkpoint blockade (ICB) as a promising treatment for Pancreatic adenocarcinoma (PAAD), there is still a need to identify specific subgroups of PAAD patients who may benefit more from ICB. T cell-mediated tumor killing (TTK) is the primary concept behind ICB. We explored subtypes according to genes correlated with the sensitivity to TKK and unraveled their underlying associations for PAAD immunotherapies.
Methods:
Genes that control the responsiveness of T cell-induced tumor destruction (GSTTK) were examined in PAAD, focusing on their varying expression levels and association with survival results. Moreover, samples with PAAD were separated into two subsets using unsupervised clustering based on GSTTK. Variability was evident in the tumor immune microenvironment, genetic mutation, and response to immunotherapy among different groups. In the end, we developed TRGscore, an innovative scoring system, and investigated its clinical and predictive significance in determining sensitivity to immunotherapy.
Results:
Patients with PAAD were categorized into 2 clusters based on the expression of 52 GSTTKs, which showed varying levels and prognostic relevance, revealing unique TTK patterns. Survival outcome, immune cell infiltration, immunotherapy responses, and functional enrichment are also distinguished among the two clusters. Moreover, we found the CATSPER1 gene promotes the progression of PAAD through experiments. In addition, the TRGscore effectively predicted the responses to chemotherapeutics or immunotherapy in patients with PAAD and overall survival.
Conclusions:
TTK exerted a vital influence on the tumor immune environment in PAAD. A greater understanding of TIME characteristics was gained through the evaluation of the variations in TTK modes across different tumor types. It highlights variations in the performance of T cells in PAAD and provides direction for improved treatment approaches.
Insights
Identifying patient subgroups is key for pancreatic adenocarcinoma (PAAD) immune checkpoint blockade (ICB) success. This study reveals distinct T cell-mediated tumor killing (TTK) patterns in PAAD, aiding personalized immunotherapy strategies.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Immune checkpoint blockade (ICB) shows promise for pancreatic adenocarcinoma (PAAD), but patient stratification is needed.
- T cell-mediated tumor killing (TTK) is central to ICB efficacy.
- Identifying specific PAAD patient subgroups likely to benefit from ICB is crucial.
Purpose of the Study:
- To explore PAAD subtypes based on genes associated with TTK sensitivity.
- To understand the link between TTK-related genes and PAAD immunotherapy response.
- To develop a predictive scoring system for immunotherapy sensitivity in PAAD.
Main Methods:
- Examined genes controlling T cell-induced tumor destruction (GSTTK) in PAAD.
- Utilized unsupervised clustering to divide PAAD samples into two subsets based on GSTTK.
- Developed and validated the TRGscore for predicting immunotherapy and chemotherapeutic response.
Main Results:
- Identified two PAAD clusters with distinct TTK patterns, prognostic relevance, and immune microenvironment characteristics.
- Observed significant differences in survival, immune cell infiltration, and immunotherapy response between clusters.
- The TRGscore accurately predicted patient response to immunotherapy and chemotherapy, and overall survival.
Conclusions:
- TTK significantly impacts the tumor immune microenvironment (TIME) in PAAD.
- Understanding variations in TTK modes enhances knowledge of TIME characteristics.
- This research provides insights into T cell function in PAAD, guiding improved treatment strategies.
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