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Immunotherapy in Upper GI Malignancies

  • Upper Gastrointestinal Cancers (L Rajdev, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

A comprehensive analysis of the interactions that can occur amongst three complex systems—the tumor cell, tissue microenvironment, and the immune response, is required if we are to realize the potential of immunotherapeutics in gastroesophageal cancer. For many years, epithelial cancers were believed to originate due to the transformation of tissue stem cells. Recently however, it has suggested that bone marrow-derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. The link between infection, chronic inflammation, and cancer has long been recognized in gastric cancer with its close association with Helicobacter pylori as a class I carcinogen. The long-term consequences of recruiting pluripotent cells to areas of chronic inflammation which can result in altered cell signaling and differentiation needs to be defined, but this work provides a fascinating insight into the pivotal role played by the immune system in the development of upper GI tumors. Here, we discuss many of the immunotherapeutic strategies that have been assessed in gastroesophageal cancer in the last two decades. At the time of writing, the use of checkpoint inhibitors represents the most exciting approach and displays the greatest potential for widespread adoption in the clinic. Preliminary data suggest that programmed death ligand-1 (PD-L1) expression ranges from approximately 18 to 42 % in gastroesophageal cancer. Phase II and phase III clinical trials involving either single agent PD-1/PD-L1 inhibition or combined with CTLA-4 inhibitors are currently enrolling, and it is expected that checkpoint inhibition will become a new standard of care in the management of advanced disease in the near future.

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Conflict of Interest

Adrian Murphy and Ronan J. Kelly declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Upper Aerodigestive Malignancies Division, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    Adrian Murphy MD & Ronan J. Kelly MD

  2. Gastroesophageal Cancer Therapeutics Program, The Bunting Blaustein Cancer Research Building, The Sidney Kimmel Comprehensive Cancer Center Johns Hopkins, 1650 Orleans Street, Room G93, Baltimore, MD, 21231, USA

    Ronan J. Kelly MD

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  1. Adrian Murphy MD
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Correspondence to Ronan J. Kelly MD.

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This article is part of the Topical Collection on Upper Gastrointestinal Cancers.

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Murphy, A., Kelly, R.J. Immunotherapy in Upper GI Malignancies. Curr. Treat. Options in Oncol. 16, 20 (2015). https://doi.org/10.1007/s11864-015-0336-6

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