4.7 Article

Can local radiotherapy and IL-12 synergise to overcome the immunosuppressive tumor microenvironment and allow in situ tumor vaccination?

期刊

CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 66, 期 7, 页码 833-840

出版社

SPRINGER
DOI: 10.1007/s00262-017-2000-4

关键词

Abscopal effect; In situ tumor vaccination; Radio-immunotherapy; Combinatorial approach; IL-12

资金

  1. INSERM (Institut National de la sante et de la recherche medicale)
  2. faculte de medecine Paris VI

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The abscopal effect, which is the spontaneous regression of tumors or metastases outside the radiation field, occurs rarely in cancer patients. Interestingly, radiotherapy (RT) triggers an immunogenic cell death (ICD) that is able to generate tumor-specific cytotoxic CD8(+) T cells that are efficient in killing cancer cells. The key question is: why is this abscopal effect so uncommon in cancer patients treated with RT? Most probably, the main reason may be related to the highly immunosuppressive tumor microenvironment of well-established tumors that constantly antagonizes the anti-tumor immune responses triggered by RT. In this case, additional or combinatorial immunotherapy is needed to attenuate these immunosuppressive networks and, therefore, substantially increases the efficacy of RT. Here, we describe a potentially promising synergistic radio-immunotherapy in situ tumor vaccination protocol by antagonizing the tumor-immunosuppressive microenvironment with a combinatorial approach using local RT and IL-12-based TH1 response augmentation.

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