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

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...

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Bibliographic Details
Main Authors: Sayeda Yasmin-Karim, Patrick T. Bruck, Michele Moreau, Sijumon Kunjachan, Gui Zhen Chen, Rajiv Kumar, Stephanie Grabow, Stephanie K. Dougan, Wilfred Ngwa
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-09-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.02030/full
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Summary: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.
ISSN:1664-3224