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Effets de la combinaison de la doxorubicine et de l’interférence avec la NTN1 sur la progression tumorale et l’infiltrat immunitaire de l’ostéosarcome

Abstract : Purpose: Despite the intensification of chemotherapies regimen, 5 years survival for patients with metastatic or relapsed osteosarcoma (OsA) remains poor. The secreted factor netrin 1 (NTN1) is overexpressed in many human cancers as a survival factor. We investigated here the role of anti NTN1 Ab in osteosarcoma. Experimental design: NTN1 expression was quantified by RT qPCR from human OsA cohort (n = 22). Anti-tumoral and anti-metastatic efficiency of anti NTN1 antibody alone or combined with doxorubicin was analyzed on a progressive and on a relapsed orthotopic and metastatic rat OsA model. Treatment effects on tumor microenvironment were performed by immuno-histological analyzes.Results: NTN1 mRNA is highly expressed in human OsA samples and in rat OsA model. Combined treatment (Dox + aNTN1 Ab) was found able to synergistically to down tumor progression, prevents tumor dissemination, and delays OsA relapse. Dox + aNTN1 Ab decreased T effetors infiltration and inhibited M2 macrophages migration in the center of rat OsA.Conclusion: NTN1 blockade potentiates chemotherapy efficacy in rat OsA models by modifications in tumor microenvironment
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https://tel.archives-ouvertes.fr/tel-01737608
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Submitted on : Monday, March 19, 2018 - 3:52:08 PM
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Morgane Monchanin. Effets de la combinaison de la doxorubicine et de l’interférence avec la NTN1 sur la progression tumorale et l’infiltrat immunitaire de l’ostéosarcome. Cancer. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1271⟩. ⟨tel-01737608⟩

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