期刊
CLINICAL CANCER RESEARCH
卷 27, 期 21, 页码 5912-5921出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-20-3925
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资金
- MD Anderson Pancreatic Cancer Moon Shot Program
- Khalifa Bin Zayed Al-Nahyan Foundation
- NIH [U01CA196403, U01CA200468, P50CA221707, R01CA227518-01A1, U54CA096300, U54CA096297, T32CA217789, T32CA009599]
- Cancer Prevention and Research Institute of Texas [CPRIT RR140012]
- Mark Foundation
- V Foundation [V201522]
- Kimmel Foundation
- McNair Foundation
- Reaumond Family Foundation
- German Research Foundation [SE-2616/2-1]
This study uses single-cell RNA sequencing to analyze the heterogeneity of pancreatic ductal adenocarcinoma, identifying different components in the tumor microenvironment and predicting multiple potential immunotherapy targets.
Purpose: Precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC) are imperative for improving disease outcomes. With molecular subtypes of PDAC gaining relevance in the context of therapeutic stratification, the ability to characterize heterogeneity of cancer-specific gene expression patterns is of great interest. In addition, understanding patterns of immune evasion within PDAC is of importance as novel immunotherapeutic strategies are developed. Experimental Design: Single-cell RNA sequencing (scRNA-seq) is readily applicable to limited biopsies from human primary and metastatic PDAC and identifies most cancers as being an admixture of previously described epithelial transcriptomic subtypes. Results: Integrative analyses of our data provide an in-depth characterization of the heterogeneity within the tumor microenvironment, including cancer-associated fibroblast subclasses, and predicts for a multitude of ligand-receptor interactions, revealing potential targets for immunotherapy approaches. Conclusions: Our analysis demonstrates that the use of de novo biopsies from patients with PDAC paired with scRNA-seq may facilitate therapeutic prediction from limited biopsy samples.
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