Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies

Jaewon J. Lee; Vincent Bernard; Alexander Semaan; Maria E. Monberg; Jonathan Huang; Bret M. Stephens; Daniel Lin; Kimal I. Rajapakshe; Brian R. Weston; Manoop S. Bhutani; Cara L. Haymaker; Chantale Bernatchez; Cullen M. Taniguchi; Anirban Maitra; Paola A. Guerrero

doi:10.1158/1078-0432.CCR-20-3925

Back

Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies

Journal article

Open access

Peer reviewed

Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies

Jaewon J. Lee, Vincent Bernard, Alexander Semaan, Maria E. Monberg, Jonathan Huang, Bret M. Stephens, Daniel Lin, Kimal I. Rajapakshe, Brian R. Weston, Manoop S. Bhutani, …

Clinical cancer research, Vol.27(21), pp.5912-5921

11/01/2021

DOI: 10.1158/1078-0432.CCR-20-3925

PMCID: PMC8563410

PMID: 34426439

Files and links (1)

url

https://doi.org/10.1158/1078-0432.CCR-20-3925View

Published (Version of record) Open Access

Abstract

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.

Life Sciences & Biomedicine

Oncology

Science & Technology

Details

Title: Subtitle: Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies
Creators: Jaewon J. Lee - The University of Texas MD Anderson Cancer Center
Vincent Bernard - The University of Texas MD Anderson Cancer Center
Alexander Semaan - The University of Texas MD Anderson Cancer Center
Maria E. Monberg - The University of Texas MD Anderson Cancer Center
Jonathan Huang - The University of Texas MD Anderson Cancer Center
Bret M. Stephens - The University of Texas MD Anderson Cancer Center
Daniel Lin - The University of Texas MD Anderson Cancer Center
Kimal I. Rajapakshe - The University of Texas MD Anderson Cancer Center
Brian R. Weston - The University of Texas MD Anderson Cancer Center
Manoop S. Bhutani - The University of Texas MD Anderson Cancer Center
Cara L. Haymaker - The University of Texas MD Anderson Cancer Center
Chantale Bernatchez - The University of Texas MD Anderson Cancer Center
Cullen M. Taniguchi - The University of Texas MD Anderson Cancer Center
Anirban Maitra - The University of Texas MD Anderson Cancer Center
Paola A. Guerrero - The University of Texas MD Anderson Cancer Center
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.27(21), pp.5912-5921
DOI: 10.1158/1078-0432.CCR-20-3925
PMID: 34426439
PMCID: PMC8563410
ISSN: 1078-0432
eISSN: 1557-3265
Publisher: Amer Assoc Cancer Research
Number of pages: 10
Grant note: German Research Foundation; German Research Foundation (DFG) NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA MD Anderson Pancreatic Cancer Moon Shot Program CPRIT RR140012; V2015-22 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA McNair Foundation SE-2616/2-1 / Reaumond Family Foundation T32CA009599 / Khalifa Bin Zayed Al-Nahyan Foundation Cancer Prevention and Research Institute of Texas; Cancer Prevention & Research Institute of Texas Kimmel Foundation
Language: English
Date published: 11/01/2021
Academic Unit: Surgery
Record Identifier: 9985240894502771

Metrics

2 Record Views