Radiation and Local Anti-CD40 Generate an Effective in situ Vaccine in Preclinical Models of Pancreatic Cancer

Front Immunol. 2018 Sep 7:9:2030. doi: 10.3389/fimmu.2018.02030. eCollection 2018.


Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an in situ vaccine. In practice, this abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a single dose of stereotactic body radiation therapy (SBRT) synergizes with intratumoral injection of agonistic anti-CD40, resulting in regression of non-treated contralateral tumors and formation of long-term immunologic memory. Long-term survival was not observed when mice received multiple fractions of SBRT, or when TGFβ blockade was combined with SBRT. SBRT and anti-CD40 was so effective at augmenting T cell priming, that memory CD8 T cell responses to both tumor and self-antigens were induced, resulting in vitiligo in long-term survivors.

Keywords: CD40; abscopal effect; immunotherapy; pancreatic cancer; radiotherapy; vitiligo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents, Immunological / pharmacology*
  • CD40 Antigens / antagonists & inhibitors*
  • CD40 Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Disease Models, Animal
  • Dose-Response Relationship, Radiation
  • Drug Evaluation, Preclinical
  • Female
  • Immunotherapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Mice
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / therapy
  • Radiation, Ionizing*
  • Radiosurgery
  • Treatment Outcome
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • CD40 Antigens
  • Cancer Vaccines