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• W3138448209 endingPage "e002022" @default.
• W3138448209 startingPage "e002022" @default.
• W3138448209 abstract "Limited therapeutic options are available for triple-negative breast cancer (TNBC), emphasizing an urgent need for more effective treatment approaches. The development of strategies by targeting tumor-associated macrophages (TAMs) to stimulate their ability of Programmed Cell Removal (PrCR) provides a promising new immunotherapy for TNBC treatment.CD47 is a critical self-protective don't eat me signal on multiple human cancers against macrophage immunosurveillance. Using human and mouse TNBC preclinical models, we evaluated the efficacy of PrCR-based immunotherapy by blocking CD47. We performed high-throughput screens on FDA-approved anti-cancer small molecule compounds for agents potentiating PrCR and enhancing the efficacy of CD47-targeted therapy for TNBC treatment.We showed that CD47 was widely expressed on TNBC cells and TAMs represented the most abundant immune cell population in TNBC tumors. Blockade of CD47 enabled PrCR of TNBC cells, but the efficacy was not satisfactory. Our high-throughput screens identified cabazitaxel in enhancing PrCR-based immunotherapy. A combination of CD47 blockade and cabazitaxel treatment yielded a highly effective treatment strategy, promoting PrCR of TNBC cells and inhibiting tumor development and metastasis in preclinical models. We demonstrated that cabazitaxel potentiated PrCR by activating macrophages, independent of its cytotoxicity toward cancer cells. When treated with cabazitaxel, the molecular and phenotypic signatures of macrophages were polarized toward M1 state, and the NF-kB signaling pathway became activated.The combination of CD47 blockade and macrophage activation by cabazitaxel synergizes to vastly enhance the elimination of TNBC cells. Our results show that targeting macrophages is a promising and effective strategy for TNBC treatment." @default.
• W3138448209 created "2021-03-29" @default.
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• W3138448209 date "2021-03-01" @default.
• W3138448209 modified "2023-10-18" @default.
• W3138448209 title "Effect of cabazitaxel on macrophages improves CD47-targeted immunotherapy for triple-negative breast cancer" @default.
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• W3138448209 doi "https://doi.org/10.1136/jitc-2020-002022" @default.
• W3138448209 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7986678" @default.
• W3138448209 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33753567" @default.
• W3138448209 hasPublicationYear "2021" @default.
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