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Synergism of chemotherapy and PD-1 immune checkpoint blockade in the PyMT mammary carcinoma mouse model

ABSTRACT: Synergism of chemotherapy and PD-1 immune checkpoint blockade in the PyMT mammary carcinoma mouse model

PROVIDER: PRJNA628738 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11620581.fastq.gz	Fastqsanger.gz
	SRR11620582.fastq.gz	Fastqsanger.gz
	SRR11620583.fastq.gz	Fastqsanger.gz
	SRR11620584.fastq.gz	Fastqsanger.gz
	SRR11620585.fastq.gz	Fastqsanger.gz

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Synergism of chemotherapy and PD-1 immune checkpoint blockade in the PyMT mammary carcinoma mouse model

Project description:We studied the impact of a combination of chemotherapy and PD-1 immune checkpoint blockade on tumor progression in the PyMT mammary carcinoma mouse model compared to each treatment as monotherapy. To gain insight into the reasons underlying improved efficacy of combined chemoimmunotherapy, whole transcriptome profiling of tumors of mice receiving either a control antibody, anti-PD-1 antibody, doxorubicin chemotherapy + a control antibody or doxorubicin chemotherapy + anti-PD-1 antibody was performed via next generation mRNA sequencing, in triplicates, on a NextSeq 550 high-throughput bench top sequencer.

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Characterization of Chemotherapy-treated PyMT Liver Matrisome

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Immune Checkpoint Blockade Improves Chemotherapy in the PyMT Mammary Carcinoma Mouse Model.

Project description:Despite the success of immune checkpoint blockade in cancer, the number of patients that benefit from this revolutionary treatment option remains low. Therefore, efforts are being undertaken to sensitize tumors for immune checkpoint blockade, which includes combining immune checkpoint blocking agents such as anti-PD-1 antibodies with standard of care treatments. Here we report that a combination of chemotherapy (doxorubicin) and immune checkpoint blockade (anti-PD-1 antibodies) induces superior tumor control compared to chemotherapy and immune checkpoint blockade alone in the murine autochthonous polyoma middle T oncogene-driven (PyMT) mammary tumor model. Using whole transcriptome analysis, we identified a set of genes that were upregulated specifically upon chemoimmunotherapy. This gene signature and, more specifically, a condensed four-gene signature predicted favorable survival of human mammary carcinoma patients in the METABRIC cohort. Moreover, PyMT tumors treated with chemoimmunotherapy contained higher levels of cytotoxic lymphocytes, particularly natural killer cells (NK cells). Gene set enrichment analysis and bead-based ELISA measurements revealed increased IL-27 production and signaling in PyMT tumors upon chemoimmunotherapy. Moreover, IL-27 signaling improved NK cell cytotoxicity against PyMT cells in vitro. Taken together, our data support recent clinical observations indicating a benefit of chemoimmunotherapy compared to monotherapy in breast cancer and suggest potential underlying mechanisms.

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Differential Gene expression in the mouse mammary tumors of PyMT-Malat1 wild-type (WT), PyMT-Malat1 knockout (KO) and PyMT-Malat1 knockout with Malat1 transgene expression (TG)

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