Cancer Immunology, Immunotherapy

, Volume 62, Issue 5, pp 949–954 | Cite as

CD40 immunotherapy for pancreatic cancer

  • Robert H. VonderheideEmail author
  • David L. Bajor
  • Rafael Winograd
  • Rebecca A. Evans
  • Lauren J. Bayne
  • Gregory L. Beatty
Focussed Research Review


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.


Tumor immunity CD40 Pancreatic cancer Macrophages T cells CIMT 2012 



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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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Robert H. Vonderheide
    • 1
    • 2
    Email author
  • David L. Bajor
    • 1
    • 2
  • Rafael Winograd
    • 1
  • Rebecca A. Evans
    • 1
  • Lauren J. Bayne
    • 1
  • Gregory L. Beatty
    • 2
  1. 1.Abramson Family Cancer Research Institute, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Division of Hematology-Oncology, Department of Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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