GTN Enhances Antitumor Effects of Doxorubicin in TNBC by Targeting the Immunosuppressive Activity of PMN-MDSC.

PMN-MDSC doxorubicin glyceryl trinitrate immunotherapy nitric oxide donor triple-negative breast cancer

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
09 Jun 2023
Historique:
received: 08 05 2023
revised: 17 05 2023
accepted: 06 06 2023
medline: 28 6 2023
pubmed: 28 6 2023
entrez: 28 6 2023
Statut: epublish

Résumé

(1) Background: Immunosuppression is a key barrier to effective anti-cancer therapies, particularly in triple-negative breast cancer (TNBC), an aggressive and difficult to treat form of breast cancer. We investigated here whether the combination of doxorubicin, a standard chemotherapy in TNBC with glyceryltrinitrate (GTN), a nitric oxide (NO) donor, could overcome chemotherapy resistance and highlight the mechanisms involved in a mouse model of TNBC. (2) Methods: Balb/C-bearing subcutaneous 4T1 (TNBC) tumors were treated with doxorubicin (8 mg/Kg) and GTN (5 mg/kg) and monitored for tumor growth and tumor-infiltrating immune cells. The effect of treatments on MDSCs reprogramming was investigated ex vivo and in vitro. (3) Results: GTN improved the anti-tumor efficacy of doxorubicin in TNBC tumors. This combination increases the intra-tumor recruitment and activation of CD8

Identifiants

pubmed: 37370739
pii: cancers15123129
doi: 10.3390/cancers15123129
pmc: PMC10296121
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Qatar National Research Fund
ID : NPRP9-459-3-090
Organisme : Ligue contre le Cancer CCIR-GE
ID : 2016

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Auteurs

Nesrine Mabrouk (N)

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75006 Paris, France.
LIIC, EA7269, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Cindy Racoeur (C)

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75006 Paris, France.
LIIC, EA7269, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Jingxuan Shan (J)

Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha P.O. Box 24144, Qatar.

Aurélie Massot (A)

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75006 Paris, France.
LIIC, EA7269, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Silvia Ghione (S)

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75006 Paris, France.
LIIC, EA7269, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Malorie Privat (M)

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75006 Paris, France.
LIIC, EA7269, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Lucile Dondaine (L)

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75006 Paris, France.
LIIC, EA7269, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Elise Ballot (E)

Plateforme de Transfert en Biologie Cancérologique, Centre GFL Leclerc, 21000 Dijon, France.

Caroline Truntzer (C)

Plateforme de Transfert en Biologie Cancérologique, Centre GFL Leclerc, 21000 Dijon, France.

Romain Boidot (R)

Unit of Molecular Biology, Georges-François Leclerc Cancer Center-UNICANCER, CNRS UMR 6302, 21000 Dijon, France.

François Hermetet (F)

CRI UMR INSERM1231, 21000 Dijon, France.
UBFC, 21000 Dijon, France.

Valentin Derangère (V)

Plateforme de Transfert en Biologie Cancérologique, Centre GFL Leclerc, 21000 Dijon, France.
UBFC, 21000 Dijon, France.

Mélanie Bruchard (M)

CRI UMR INSERM1231, 21000 Dijon, France.
UBFC, 21000 Dijon, France.

Frédérique Végran (F)

Plateforme de Transfert en Biologie Cancérologique, Centre GFL Leclerc, 21000 Dijon, France.
CRI UMR INSERM1231, 21000 Dijon, France.
UBFC, 21000 Dijon, France.

Lotfi Chouchane (L)

Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha P.O. Box 24144, Qatar.

François Ghiringhelli (F)

Plateforme de Transfert en Biologie Cancérologique, Centre GFL Leclerc, 21000 Dijon, France.
CRI UMR INSERM1231, 21000 Dijon, France.
UBFC, 21000 Dijon, France.

Ali Bettaieb (A)

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75006 Paris, France.
LIIC, EA7269, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Catherine Paul (C)

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75006 Paris, France.
LIIC, EA7269, Université de Bourgogne Franche Comté, 21000 Dijon, France.

Classifications MeSH