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Etude des mécanismes d'action d'une immunothérapie par un triacyl lipide A chez l'homme

Abstract : Immunotherapy acting at the primary tumor site and preventing the development of metastases is one of the strategies for treatment of patients with cancer. To improve the efficiency of the latter, it is necessary to understand how it induces tumor cell death. In the laboratory, it was observed the cure of PROb tumors in rats BDIX by the triacyl lipid A. It has been shown that this effect involved the immune system involving interactions with TLRs present in many tumor cells and innate immunity cells such as neutrophils.In this work, we investigated the possible involvement of neutrophils in the antitumor activity of triacyl lipid A in humans.In a Phase 1 study in patients with refractory solid tumors, we showed that the triacyl lipid A was well tolerated and induced the secretion of cytokines involved in the immune response, particularly in the recruitment of neutrophils. Then, in a second part, we demonstrated the prospective involvement of neutrophils in the immune response by checking their presence in human colon cancers and analyzing their proximity to tumor cells, these two factors determining their cytotoxicity to cells tumor. Then we made a comparative analysis with healthy tissue to research whether these neutrophils were activated and compare the expression of chemo attractors.
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Submitted on : Monday, March 31, 2014 - 10:22:43 AM
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  • HAL Id : tel-00967908, version 1



Nicolas Isambert. Etude des mécanismes d'action d'une immunothérapie par un triacyl lipide A chez l'homme. Médecine humaine et pathologie. Université de Bourgogne, 2013. Français. ⟨NNT : 2013DIJOMU03⟩. ⟨tel-00967908⟩



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