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Pancreatic Cancer pp 481–508Cite as

Stromal Inflammation in Pancreatic Cancer: Mechanisms and Translational Applications

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Abstract

Pancreatic ductal adenocarcinoma is the most severe form of pancreatic cancer because of pronounced inflammation and desmoplasia leading to hypoxia, metabolic reprogramming, and immune suppression that ultimately promote tumor growth and metastasis. The conventional wisdom is that patient survival is hobbled by the inability of currently available therapies to penetrate the tumor and its dense stromal microenvironment. The pancreatic cancer stromal microenvironment is a heterogeneous population of cancer cells, immune cells, cancer-associated fibroblasts, vascular endothelial cells, and neurons. While a detailed understanding of the cells, mediators, and receptors influencing stromal dynamism continues to emerge, interactions between these cells influence tumor suppression as well as tumor promotion. The specific roles for the inflamed stroma in pancreatic cancer immune evasion, progression, metastasis, and therapeutic resistance likely depend on stage of tumor development and distinct biophysical features within the dynamic cellular micro-niches of the tumor. Uncovering the stromal mechanisms of tumor development and progression should prompt the discovery of key windows of opportunity for multimodal therapies in pancreatic cancer.

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Acknowledgments

The authors thank past and present members of the Dwinell Laboratory as well as Dr. Ishan Roy, Dr. Bryon Johnson, and Dr. Edna Cukierman for constructive conversations about mucosal inflammation and stromal interactions within the pancreatic cancer microenvironment. Work in the laboratory is supported by the National Cancer Institute (U01 CA178960) and continuing philanthropic support from the Bobbie Nick Voss Charitable Foundation and the We Care Fund. The authors gratefully acknowledge and apologize to numerous colleagues whose excellent work could not be cited due to space restrictions.

In memory of Martin F. Kagnoff, MD who succumbed to complications of pancreatic cancer in 2014. His enduring legacy and passion for understanding the pathophysiologic mechanisms of mucosal inflammation remain an inspiration to his trainees and colleagues.

Disclosures MBD is cofounder and has financial interests in Protein Foundry, LLC, a biotech startup that manufactures recombinant chemokines for biomedical research. MBD has been granted a patent [US Patent 8,404,640] for the use of recombinant CXCL12 as an antitumor agent.

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Authors and Affiliations

  1. Pancreatic Cancer Program, Department of Microbiology and Immunology, MCW Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, USA

    Kathleen A. Boyle & Michael B. Dwinell

  2. Pancreatic Cancer Program, Department of Surgery, MCW Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, USA

    Michael A. James, Susan Tsai, Douglas B. Evans & Michael B. Dwinell

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  1. Kathleen A. Boyle
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  2. Michael A. James
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  3. Susan Tsai
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  4. Douglas B. Evans
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  5. Michael B. Dwinell
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Correspondence to Michael B. Dwinell .

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Editors and Affiliations

  1. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    John P. Neoptolemos

  2. Division of Research Department of Surgery and Genomic Sciences and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Raul Urrutia

  3. Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA

    James L. Abbruzzese

  4. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    Markus W. Büchler

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Boyle, K.A., James, M.A., Tsai, S., Evans, D.B., Dwinell, M.B. (2018). Stromal Inflammation in Pancreatic Cancer: Mechanisms and Translational Applications. In: Neoptolemos, J., Urrutia, R., Abbruzzese, J., Büchler, M. (eds) Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7193-0_55

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