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Breast Cancer Stem Cells Regulated Metabolism Remodeling of Bulk Tumor Cells Drives Immune Evasion

ABSTRACT: Breast Cancer Stem Cells Regulated Metabolism Remodeling of Bulk Tumor Cells Drives Immune Evasion

PROVIDER: PRJNA910536 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22588010_1.fastq.gz	Fastqsanger.gz
	SRR22588010_2.fastq.gz	Fastqsanger.gz
	SRR22588011_1.fastq.gz	Fastqsanger.gz
	SRR22588011_2.fastq.gz	Fastqsanger.gz
	SRR22588012_1.fastq.gz	Fastqsanger.gz

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Breast Cancer Stem Cells Regulated Metabolism Remodeling of Bulk Tumor Cells Drives Immune Evasion

Project description:Reprogramming of energy metabolism plays pivotal roles in cancer progression and immune surveillance. Here, we demonstrated that breast cancer cells showed positive feedback enhanced aerobic glycolysis in hypoxia condition. Further investigation suggested that breast cancer stem cells (BCSCs) induced by hypoxia stimulate aerobic glycolysis in bulk tumor cells. Cells cultured with hypoxic tumor cell- or BCSC-secretome exhibited similar gene expression patterns, with global remodeling of metabolism pathways, particularly glycolysis. BCSCs regulated glycolysis promoted breast cancer progression and evasion of immune surveillance. Screening of BCSC secretome identified MIF as a pivotal factor that potentiated glycolysis by increasing the expression of ALDOC. Breast cancer cell–intrinsic MIF depletion inhibited tumor progression and augmented intratumoral cytolytic CD8+ T cells and pro-inflammatory macrophages. Targeting MIF optimized immune checkpoint therapy of breast cancer in both syngeneic mouse models and humanized mouse model. Hence, this study delineates the contribution of BCSC regulated bulk tumor cell glycolysis in immune surveillance; and thereby proposes strategies to optimize immunotherapy in breast cancer.

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Breast Cancer Stem Cells Regulated Metabolism Remodeling of Bulk Tumor Drives Immune Evasion

Project description:Breast Cancer Stem Cells Regulated Metabolism Remodeling of Bulk Tumor Drives Immune Evasion

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Breast Cancer Stem Cells Regulated Metabolism Remodeling of Bulk Tumor Drives Immune Evasion

Project description:Reprogramming of energy metabolism plays pivotal roles in cancer progression and immune surveillance. Here, we demonstrated that hypoxic cancer cell secretome and breast cancer stem cell (BCSC) secretome similarly promoted the global reprogramming of metabolic pathways, particularly glycolysis, in normoxic cancer cells. Screening of BCSC secretome identified MIF as a pivotal factor potentiating glycolysis via transcriptional activation of ALDOC expression by MYC. Targeting MIF attenuated glycolysis as well as impaired tumor growth and metastasis. Cell-intrinsic MIF depletion in breast cancer augmented intratumoral cytolytic CD8+ T cells and pro-inflammatory macrophages while decreased tumor-associated neutrophils. Targeting MIF improved anti-PD-L1 immune checkpoint therapy of triple-negative breast cancer cells. Hence, this study presented a paradigm of heterocellular metabolic communication in modulating tumor energy metabolism and immune surveillance, and thereby proposes strategies to ameliorate immunotherapy in breast cancer.

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