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CD40 immunotherapy for pancreatic cancer

  • Focussed Research Review
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive and lethal cancer which is poorly responsive to standard therapies. Although the PDA tumor microenvironment is considered especially immunosuppressive, recent data mostly from genetically engineered and other mouse models of the disease suggest that novel immunotherapeutic approaches hold promise. Here, we describe both laboratory and clinical efforts to target the CD40 pathway for immunotherapy in PDA. Findings suggest that CD40 agonists can mediate both T-cell-dependent and T-cell-independent immune mechanisms of tumor regression in mice and patients. T-cell-independent mechanisms are associated with macrophage activation and the destruction of PDA tumor stroma, supporting the concept that immune modulation of the tumor microenvironment represents a useful approach in cancer immunotherapy.

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Acknowledgments

We thank Ben Stanger, Andrew Rhim, Anil Rustgi, Peter O’Dwyer, and Ursina Teitelbaum for helpful discussions. This work was supported by grants from the National Institutes of Health (R01 CA158186 and R01 CA169123, to Robert H. Vonderheide; T32 HL007775 to David L Bajor; and K08 CA138907 to Gregory L Beatty).

Conflict of interest

The authors declare that they have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, 8-121 Smilow Center for Translational Research, 3400 Civic Center Blvd, Philadelphia, PA, 19104-5156, USA

    Robert H. Vonderheide, David L. Bajor, Rafael Winograd, Rebecca A. Evans & Lauren J. Bayne

  2. Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Robert H. Vonderheide, David L. Bajor & Gregory L. Beatty

Authors
  1. Robert H. Vonderheide
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  2. David L. Bajor
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  3. Rafael Winograd
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  4. Rebecca A. Evans
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  5. Lauren J. Bayne
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  6. Gregory L. Beatty
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Corresponding author

Correspondence to Robert H. Vonderheide.

Additional information

This paper is a Focussed Research Review based on a presentation given at the 10th annual meeting of the association for cancer immunotherapy (CIMT), held in Mainz, Germany, May 23 to 25, 2012. It is part of a CII series of Focussed Research Reviews and meeting report.

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Vonderheide, R.H., Bajor, D.L., Winograd, R. et al. CD40 immunotherapy for pancreatic cancer. Cancer Immunol Immunother 62, 949–954 (2013). https://doi.org/10.1007/s00262-013-1427-5

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  • DOI: https://doi.org/10.1007/s00262-013-1427-5

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