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Co-targeting TGF-β and PD-L1 sensitizes triple-negative breast cancer to experimental immunogenic cisplatin-eribulin chemotherapy doublet
by
Limagne, Emeric
, Bellaye, Pierre-Simon
, Thibaudin, Marion
, Ladoire, Sylvain
, Rialland, Mickaël
, Kalfeist, Laura
, Petit, Stacy
, Aucagne, Romain
, Truntzer, Caroline
, Ilie, Alis
, Kada Mohammed, Samia
, Ledys, Fanny
, Derangère, Valentin
, Galland, Loïck
, Poirrier, Cyriane
, Rageot, David
, Ghiringhelli, François
in
Animals
/ Antineoplastic Combined Chemotherapy Protocols - pharmacology
/ B7-H1 Antigen - antagonists & inhibitors
/ B7-H1 Antigen - immunology
/ Cell Line, Tumor
/ Cisplatin - administration & dosage
/ Cisplatin - pharmacology
/ Female
/ Furans - administration & dosage
/ Furans - pharmacology
/ Humans
/ Immunology
/ Ketones - administration & dosage
/ Ketones - pharmacology
/ Mice
/ Neoplasm Proteins - antagonists & inhibitors
/ Neoplasm Proteins - immunology
/ Oncology
/ Polyether Polyketides
/ Transforming Growth Factor beta - antagonists & inhibitors
/ Transforming Growth Factor beta - immunology
/ Triple Negative Breast Neoplasms - drug therapy
/ Triple Negative Breast Neoplasms - immunology
/ Triple Negative Breast Neoplasms - pathology
2025
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Co-targeting TGF-β and PD-L1 sensitizes triple-negative breast cancer to experimental immunogenic cisplatin-eribulin chemotherapy doublet
by
Limagne, Emeric
, Bellaye, Pierre-Simon
, Thibaudin, Marion
, Ladoire, Sylvain
, Rialland, Mickaël
, Kalfeist, Laura
, Petit, Stacy
, Aucagne, Romain
, Truntzer, Caroline
, Ilie, Alis
, Kada Mohammed, Samia
, Ledys, Fanny
, Derangère, Valentin
, Galland, Loïck
, Poirrier, Cyriane
, Rageot, David
, Ghiringhelli, François
in
Animals
/ Antineoplastic Combined Chemotherapy Protocols - pharmacology
/ B7-H1 Antigen - antagonists & inhibitors
/ B7-H1 Antigen - immunology
/ Cell Line, Tumor
/ Cisplatin - administration & dosage
/ Cisplatin - pharmacology
/ Female
/ Furans - administration & dosage
/ Furans - pharmacology
/ Humans
/ Immunology
/ Ketones - administration & dosage
/ Ketones - pharmacology
/ Mice
/ Neoplasm Proteins - antagonists & inhibitors
/ Neoplasm Proteins - immunology
/ Oncology
/ Polyether Polyketides
/ Transforming Growth Factor beta - antagonists & inhibitors
/ Transforming Growth Factor beta - immunology
/ Triple Negative Breast Neoplasms - drug therapy
/ Triple Negative Breast Neoplasms - immunology
/ Triple Negative Breast Neoplasms - pathology
2025
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Co-targeting TGF-β and PD-L1 sensitizes triple-negative breast cancer to experimental immunogenic cisplatin-eribulin chemotherapy doublet
by
Limagne, Emeric
, Bellaye, Pierre-Simon
, Thibaudin, Marion
, Ladoire, Sylvain
, Rialland, Mickaël
, Kalfeist, Laura
, Petit, Stacy
, Aucagne, Romain
, Truntzer, Caroline
, Ilie, Alis
, Kada Mohammed, Samia
, Ledys, Fanny
, Derangère, Valentin
, Galland, Loïck
, Poirrier, Cyriane
, Rageot, David
, Ghiringhelli, François
in
Animals
/ Antineoplastic Combined Chemotherapy Protocols - pharmacology
/ B7-H1 Antigen - antagonists & inhibitors
/ B7-H1 Antigen - immunology
/ Cell Line, Tumor
/ Cisplatin - administration & dosage
/ Cisplatin - pharmacology
/ Female
/ Furans - administration & dosage
/ Furans - pharmacology
/ Humans
/ Immunology
/ Ketones - administration & dosage
/ Ketones - pharmacology
/ Mice
/ Neoplasm Proteins - antagonists & inhibitors
/ Neoplasm Proteins - immunology
/ Oncology
/ Polyether Polyketides
/ Transforming Growth Factor beta - antagonists & inhibitors
/ Transforming Growth Factor beta - immunology
/ Triple Negative Breast Neoplasms - drug therapy
/ Triple Negative Breast Neoplasms - immunology
/ Triple Negative Breast Neoplasms - pathology
2025
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Co-targeting TGF-β and PD-L1 sensitizes triple-negative breast cancer to experimental immunogenic cisplatin-eribulin chemotherapy doublet
Journal Article
Co-targeting TGF-β and PD-L1 sensitizes triple-negative breast cancer to experimental immunogenic cisplatin-eribulin chemotherapy doublet
2025
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Overview
In preclinical mouse models of triple-negative breast cancer (TNBC), we show that a combination of chemotherapy with cisplatin (CDDP) and eribulin (Eri) was additive from an immunological point of view and was accompanied by the induction of an intratumoral immune and inflammatory response favored by the immunogenic cell death induced by CDDP, as well as by the vascular and tumor stromal remodeling induced by each chemotherapy. Unexpectedly, despite the favorable immune context created by this immunomodulatory chemotherapy combination, our models remained refractory to the addition of anti-PD-L1 immunotherapy. These surprising observations led us to discover that CDDP chemotherapy was simultaneously responsible for the production of TGF-β by several populations of cells present in tumors, which favored the emergence of different subpopulations of immune cells and cancer-associated fibroblasts characterized by immunosuppressive properties. Accordingly, co-treatment with anti-TGF-β restored the immunological synergy between this immunogenic doublet of chemotherapy and anti-PD-L1 in a CD8-dependent manner. Translational studies revealed the unfavorable prognostic effect of the TGF-β pathway on the immune response in human TNBC, as well as the ability of CDDP to induce this cytokine also in human TNBC cell lines, thus highlighting the clinical relevance of targeting TGF-β in the context of human TNBC treated with chemoimmunotherapy.
Publisher
American Society for Clinical Investigation
Subject
/ Antineoplastic Combined Chemotherapy Protocols - pharmacology
/ B7-H1 Antigen - antagonists & inhibitors
/ Cisplatin - administration & dosage
/ Female
/ Furans - administration & dosage
/ Humans
/ Ketones - administration & dosage
/ Mice
/ Neoplasm Proteins - antagonists & inhibitors
/ Neoplasm Proteins - immunology
/ Oncology
/ Transforming Growth Factor beta - antagonists & inhibitors
/ Transforming Growth Factor beta - immunology
/ Triple Negative Breast Neoplasms - drug therapy
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