Exploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma

Bailey, P. et al. (2016) Exploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma. Scientific Reports, 6, 35848. (doi: 10.1038/srep35848) (PMID:27762323) (PMCID:PMC5071896)

Abstract

Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases. Our findings reveal that: (a) nearly all PDAC samples harbor potentially targetable neoantigens; (b) T cells are present but generally show a reduced activation signature; and (c) markers of efficient antigen presentation are associated with a reduced signature of markers characterizing cytotoxic T cells. These findings suggest that despite the presence of tumor specific neoepitopes, T cell activation is actively suppressed in PDAC. Further, we identify iNOS as a potential mediator of immune suppression that might be actionable using pharmacological avenues.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bailey, Dr Peter and Chang, Professor David and Biankin, Professor Andrew
• Authors: Bailey, P., Chang, D. K., Forget, M.-A., San Lucas, F. A., Alvarez, H. A., Haymaker, C., Chattopadhyay, C., Kim, S.-H., Ekmekcioglu, S., Grimm, E. A., Biankin, A. V., Hwu, P., Maitra, A., and Roszik, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Scientific Reports 6: 35848
• Publisher Policy: Reproduced under a Creative Commons License