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Author Notes:

Correspondence: Walid Shaib or Gregory B. Lesinski, Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, 1365 Clifton Road NE, Atlanta, Georgia 30322, USA. Phone: 404.778.1900; Email: wilad.shaib@emory.edu (WS). Phone: 404.778.3072; Email: gregory.b.lesinski@emory.edu (GBL).

MRF, LS, WS, and GBL conceived this work and participated in experimental design. LS, AK, MZ, and WS reviewed clinical records to select archival specimens to include in this study and obtained specimens from pathology. MRF and HC analyzed RNA expression profiles.

MRF, MBW, JG, YL, and GBL analyzed and acquired spatially resolved protein expression data. MRF, MBW, HC, MZ, JMS, DK, PP, WS, and GBL worked together on the interpretation of data. MRF and HC carried out statistical tests. MRF, MBW, SKM, BE, WS, and GBL took primary roles in the drafting and revisions of manuscript.

All authors edited and provided feedback on the manuscript. All authors have read and approved of this final manuscript.

Disclosures: MRF received research and travel support from NanoString Inc. JG is an employee of NanoString Inc. YL is an employee of NanoString Inc.

BE receives research support from several pharmaceutical companies (Boston Biomedical Inc., Bayer, Pfizer, Novartis, Merck, Bristol-Myers Squibb, and Roche) and consults for several companies (Astellas, Taiho, Ipsen, Novartis, Lexicon, and Roche).

WS receives research support from Boston Biomedical Inc., Eli Lilly, and Lexicon and has received honoraria from Ipsen and Eisai.

GBL has received compensation for consulting with ProDa Biotech LLC and has received research funding through sponsored research agreements between Emory University and Merck and Co. Inc., Boehringer Ingelheim Inc., Bristol-Myers Squibb Inc., and Vaccinex Inc.

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Research Funding:

This work was funded in part by in-kind grant support (materials and lab services) from NanoString Inc. as well as research funds from the Hirshberg Foundation and NIH grants R01 CA208253 and R01228406.

We would like to acknowledge the contribution of the EIGC, which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities.

Research reported in this publication was supported in part by the EIGC Shared Resource and the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/National Cancer Institute under award P30CA138292.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • Set enrichment analysis
  • Database
  • Cells

Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy

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Journal Title:

JCI Insight

Volume:

Volume 5, Number 1

Publisher:

, Pages 1-14

Type of Work:

Article | Final Publisher PDF

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) has dismal 5-year survival (<9%). We hypothesize that exposure of tumors to conventional therapies may preferentially modulate immune biomarkers in the tumor microenvironment in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. Total expression of immunologically relevant transcripts and spatially resolved expression of immunologically relevant proteins was quantitated using multiplexed methods (NanoString nCounter and GeoMX platforms). This analysis identified numerous differentially expressed transcripts associated with the type of neoadjuvant therapy received. Moreover, we identified significant alterations in the expression and/or spatial distribution of immunologically relevant proteins in different regions (tumor cell rich, immune cell rich, stromal cell rich) of the tumor microenvironment. These data provide insight into the immunological effects of clinically relevant neoadjuvant therapy for resectable/borderline-resectable PDAC by describing significant differences in the expression of key immunologic biomarkers within the PDAC microenvironment that were associated with the type of treatment patients received prior to surgical resection. This represents a comprehensive analysis of numerous biomarkers conducted on the PDAC microenvironment. This work may guide strategic new combination therapies for pancreatic cancer.

Copyright information:

© 2020, American Society for Clinical Investigation.

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