رسالة جامعية
Study of the involvement of autophagy in the acquisition of tumor resistance to Natural Killer-mediated lysis ; Etude de l'implication de l'autophagie dans l'acquisition de résistance tumorale à la lyse par les lymphocytes 'Natural Killer'
| العنوان: | Study of the involvement of autophagy in the acquisition of tumor resistance to Natural Killer-mediated lysis ; Etude de l'implication de l'autophagie dans l'acquisition de résistance tumorale à la lyse par les lymphocytes 'Natural Killer' |
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| المؤلفون: | Baginska, Joanna |
| المساهمون: | Centre de Recherche Public de la Santé, Université Paris Sud - Paris XI, Bassam Janji |
| المصدر: | https://tel.archives-ouvertes.fr/tel-01236940Test ; Cancer. Université Paris Sud - Paris XI, 2013. English. ⟨NNT : 2013PA11T088⟩. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2013 |
| المجموعة: | Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| مصطلحات موضوعية: | Innate immunity, Immunotherapy, Hypoxic tumor microenvironment, Breast adenocarcinoma, Autophagy, Autophagie, Immunité inné, Immunothérapie, Microenvironnement tumorale hypoxique, Adénocarcinome mammaire, [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | Natural killer (NK) cells are effectors of the antitumor immunity, able to kill cancer cells through the release of the cytotoxic protease granzyme B. NK-based therapies have recently emerged as promising anticancer strategies. However, it is well established that hypoxic microenvironment interferes with the function of antitumor immune cells and constitutes a major obstacle for cancer immunotherapies. Recent studies demonstrated that autophagy is an important regulator of innate immune response in this microenvironment, but the mechanism by which autophagy regulates NK cell-mediated antitumor immune responses remains elusive. Here, we demonstrate that hypoxia impairs breast cancer cell susceptibility to NK-mediated lysis in vitro via the activation of autophagy. This impairment was not related to a defect in target cell recognition by NK cells but to the degradation of NK-derived granzyme B in autophagosomes of hypoxic cells. Inhibition of autophagy by targeting beclin1 (BECN1) restored granzyme B levels in hypoxic cells in vitro and induced tumor regression in vivo by facilitating NK-mediated tumor cell killing. Together, our data highlight autophagy as a mechanism underlying the resistance of hypoxic tumor cells to NK-mediated lysis and provides a cutting-edge advance in our understanding of the underlying mechanism. This study might pave the way for the formulation of more effective NK cell-based antitumor therapies. ; Les lymphocytes « Natural Killer » (NK) sont des effecteurs de l’immunité innée, capables de lyser les cellules cancéreuses grâce au relargage de la protéase cytotoxique Granzyme B (GzmB). Récemment, de nouvelles stratégies anti-cancéreuses, basées sur l’utilisation des cellules NK, ont émergé et se sont révélées très prometteuses. Il est maintenant clairement établi que le microenvironnement tumoral hypoxique influence la réponse immunitaire et constitue, de ce fait, un obstacle majeur pour établir des protocoles d’immunothérapies efficaces. Des études récentes ont montré que l’autophagie est ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | English |
| العلاقة: | NNT: 2013PA11T088; tel-01236940; https://tel.archives-ouvertes.fr/tel-01236940Test; https://tel.archives-ouvertes.fr/tel-01236940/documentTest; https://tel.archives-ouvertes.fr/tel-01236940/file/VA_BAGINSKA_JOANNA_28112013_-_2.pdfTest; https://tel.archives-ouvertes.fr/tel-01236940/file/VA_BAGINSKA_JOANNA_28112013_Synthse.pdfTest |
| الإتاحة: | https://tel.archives-ouvertes.fr/tel-01236940Test https://tel.archives-ouvertes.fr/tel-01236940/documentTest https://tel.archives-ouvertes.fr/tel-01236940/file/VA_BAGINSKA_JOANNA_28112013_-_2.pdfTest https://tel.archives-ouvertes.fr/tel-01236940/file/VA_BAGINSKA_JOANNA_28112013_Synthse.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.914FDB9E |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |