Disrupting a converging metabolic target turns up the immunologic-heat in pancreatic tumors
Won Jin Ho1,2 and Elizabeth M. Jaffee1,2,3,4,5
1Sidney Kimmel Comprehensive Cancer Center,
2Bloomberg-Kimmel Institute for Cancer Immunotherapy,
3Pancreatic Cancer Precision Medicine Program,
4Department of Pathology, and
5Skip Viragh Center for Pancreatic Cancer, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Address correspondence to: Elizabeth M. Jaffee, 1830 East Monument Street, Room 4M07 Cancer Research Building I, Suite 2-103, Baltimore, Maryland 21205, USA. Phone: 410.955.2957; Email: ejaffee@jhmi.edu.
Find articles by Ho, W. in: JCI | PubMed | Google Scholar
1Sidney Kimmel Comprehensive Cancer Center,
2Bloomberg-Kimmel Institute for Cancer Immunotherapy,
3Pancreatic Cancer Precision Medicine Program,
4Department of Pathology, and
5Skip Viragh Center for Pancreatic Cancer, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Address correspondence to: Elizabeth M. Jaffee, 1830 East Monument Street, Room 4M07 Cancer Research Building I, Suite 2-103, Baltimore, Maryland 21205, USA. Phone: 410.955.2957; Email: ejaffee@jhmi.edu.
Find articles by
Jaffee, E.
in:
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Published December 3, 2019 - More info
J Clin Invest. 2020;130(1):71–73. https://doi.org/10.1172/JCI133685.
© 2020 American Society for Clinical Investigation
Pancreatic ductal adenocarcinomas (PDACs) are classically immunologically cold tumors that have failed to demonstrate a significant response to immunotherapeutic strategies. This feature is attributed to both the immunosuppressive tumor microenvironment (TME) and limited immune cell access due to the surrounding stromal barrier, a histological hallmark of PDACs. In this issue of the JCI, Sharma et al. employ a broad glutamine antagonist, 6-diazo-5-oxo-l-norleucine (DON), to target a metabolic program that underlies both PDAC growth and hyaluronan production. Their findings describe an approach to converting the PDAC TME into a hot TME, thereby empowering immunotherapeutic strategies such as anti-PD1 therapy.
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