دورية أكاديمية
Chemo-immunotherapy by nanoliposomal epacadostat and docetaxel combination to IDO1 inhibition and tumor microenvironment suppression.
| العنوان: | Chemo-immunotherapy by nanoliposomal epacadostat and docetaxel combination to IDO1 inhibition and tumor microenvironment suppression. |
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| المؤلفون: | Khoshkhabar R; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran., Yazdani M; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran., Hoda Alavizadeh S; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Alavizadehh@mums.ac.ir., Saberi Z; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran., Arabi L; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran., Reza Jaafari M; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Jafarimr@mums.ac.ir. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112437. Date of Electronic Publication: 2024 Jun 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Indoleamine-Pyrrole 2,3,-Dioxygenase*/antagonists & inhibitors , Indoleamine-Pyrrole 2,3,-Dioxygenase*/metabolism , Docetaxel*/pharmacology , Docetaxel*/therapeutic use , Tumor Microenvironment*/drug effects , Tumor Microenvironment*/immunology , Liposomes* , Melanoma, Experimental*/drug therapy , Melanoma, Experimental*/immunology , Sulfonamides*/pharmacology , Sulfonamides*/administration & dosage , Sulfonamides*/therapeutic use , Mice, Inbred C57BL*, Animals ; Mice ; Cell Line, Tumor ; Immunotherapy/methods ; Oximes/pharmacology ; Oximes/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; Female ; Nanoparticles ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use |
| مستخلص: | The over-activation of tryptophan (Trp) metabolism to kynurenine (Kyn) catalyzed by Indoleamine 2,3-dioxygenase-1 (IDO1) enzyme, is one of the main metabolic pathways involved in tumor microenvironment (TME) immune escape and cancer treatment failure. The most efficient of IDO1 inhibitors is Epacadostat (EPA). Since monotherapy with single-agent IDO1 inhibitor regimen has led to an insufficient anti-tumor activity, we examined the efficacy of simultaneous treatment by Liposomal epacadostat (Lip-EPA) as a potent IDO inhibitor, in combination with docetaxel (DTX) as a complement immunogenic cell death (ICD) agent against B16F10 model. First, the in vitro combination index (CI) of epacadostat (EPA) and DTX was investigated by using the unified theory. Then, the in vivo efficacy of the combination therapy was assessed. Results indicated the synergestic cytotoxic effect of the combination on B16F10 compared to normal fibroblast cells (NIH). The immune profiling demonstrated a significant increase in the percentage of infiltrated T lymphocytes and IFN-γ release, a significant decrease in the percentage of regulatory T cells (Treg) population and the subsequent low levels of IL-10 generation in mice treated with Lip-EPA + DTX. Further, a significant tumor growth delay (TGD = 69.15 %) and an increased life span (ILS > 47.83 %) was observed with the combination strategy. Histopathology analysis revealed a remarkable increase in the Trp concentration following combination treatment, while Kyn levels significantly decreased. Results showed that the nano-liposomal form of IDO1 inhibitor in combination with chemotherapy could significantly improve the imunity response and dominate the tumor immuno-suppressive micro-environment, which merits further investigations. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Chemo-immunotherapy; Docetaxel; IDO1 inhibitor; Melanoma; Tumor microenvironment |
| المشرفين على المادة: | 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) 15H5577CQD (Docetaxel) 0 (Liposomes) 71596A9R13 (epacadostat) 0 (Sulfonamides) 0 (IDO1 protein, mouse) 0 (Oximes) 0 (Antineoplastic Agents) |
| تواريخ الأحداث: | Date Created: 20240613 Date Completed: 20240710 Latest Revision: 20240710 |
| رمز التحديث: | 20240710 |
| DOI: | 10.1016/j.intimp.2024.112437 |
| PMID: | 38870880 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2024.112437 |