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

Autor: Sayeda Yasmin-Karim, Patrick T. Bruck, Michele Moreau, Sijumon Kunjachan, Gui Zhen Chen, Rajiv Kumar, Stephanie Grabow, Stephanie K. Dougan, Wilfred Ngwa
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Frontiers in Immunology, Vol 9 (2018)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2018.02030
Popis: 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.
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