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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
GTN Enhances Antitumor Effects of Doxorubicin in TNBC by Targeting the Immunosuppressive Activity of PMN-MDSC
Cancers, Volume 15, No. 12, Article 3129, Year 2023
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Description
(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+ lymphocytes and dampens the immunosuppressive function of PMN-MDSCs PD-L1low. Mechanistically, in PMN-MDSC, the doxorubicin/GTN combination reduced STAT5 phosphorylation, while GTN +/− doxorubicin induced a ROS-dependent cleavage of STAT5 associated with a decrease in FATP2. (4) Conclusion: We have identified a new combination enhancing the immune-mediated anticancer therapy in a TNBC mouse model through the reprograming of PMN-MDSCs towards a less immunosuppressive phenotype. These findings prompt the testing of GTN combined with chemotherapies as an adjuvant in TNBC patients experiencing treatment failure. © 2023 by the authors.
Authors & Co-Authors
Racoeur, Cindy
France, Paris
Université Psl
France, Dijon
Laboratoire D'immunologie et Immunothérapie Des Cancers
Shan, Jingxuan
Qatar, Doha
Weill Cornell Medicine-qatar
Dondaine, Lucile
France, Paris
Université Psl
France, Dijon
Laboratoire D'immunologie et Immunothérapie Des Cancers
Truntzer, Caroline
Unknown Affiliation
Boidot, Romain
France, Dijon
Icmub Institut de Chimie Moléculaire de L'université de Bourgogne
Hermetet, François
France, Besancon
Université Bourgogne Franche-comté
Dérangère, Valentin
France, Besancon
Université Bourgogne Franche-comté
Bruchard, Mélanie
France, Besancon
Université Bourgogne Franche-comté
Végran, Frédérique
France, Besancon
Université Bourgogne Franche-comté
Chouchane, Lotfi
Qatar, Doha
Weill Cornell Medicine-qatar
Ghiringhelli, François
France, Besancon
Université Bourgogne Franche-comté
Bettaïeb, Ali
France, Paris
Université Psl
France, Dijon
Laboratoire D'immunologie et Immunothérapie Des Cancers
Paul, Catherine
France, Paris
Université Psl
France, Dijon
Laboratoire D'immunologie et Immunothérapie Des Cancers
Statistics
Authors: 13
Affiliations: 5
Identifiers
Doi:
10.3390/cancers15123129
ISSN:
20726694
Research Areas
Cancer