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Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer

ABSTRACT: Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer

PROVIDER: PRJNA734581 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14711335.fastq.gz	Fastqsanger.gz
	SRR14711336.fastq.gz	Fastqsanger.gz
	SRR14711337.fastq.gz	Fastqsanger.gz
	SRR14711338.fastq.gz	Fastqsanger.gz
	SRR14711339.fastq.gz	Fastqsanger.gz

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Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer [sequencing]

Project description:Radiation therapy induces immunogenic cell death in cancer cells, whereby apoptotic cells release endogenous adjuvants that are sensed by immune cells to direct adaptive immune responses. Toll-like receptors (TLRs) expressed on several immune subtypes recognize these products to direct downstream responses in part via the adapter protein MyD88. Here we use lineage specific deletion of Myd88 to interrogate its contribution to the immune response to radiation therapy in distinct immune populations in pancreatic cancer. While Myd88 deletion in Itgax- and Lck-expressing immune populations had little discernable effects on response to radiation therapy, Lyz2-specific loss of Myd88 rendered tumors more susceptible to radiation therapy dependent on CD8+ T cells. scRNAseq revealed gene signatures in myeloid and dendritic cells indicative of enhanced type I and II interferon responses. Together, these data implicate MyD88 signaling in myeloid cells as a critical source of immunosuppression that hinders adaptive immune tumor control following radiation therapy.

2023-08-28 | GSE176011 | GEO

Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer [Nanostring]

2023-08-28 | GSE176014 | GEO

Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer [sequencing]

Project description:Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer [sequencing]

| PRJNA734576 | ENA

Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer [Nanostring]

Project description:Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer [Nanostring]

| PRJNA734585 | ENA

Myeloid MyD88 restricts CD8<sup>+</sup> T cell response to radiation therapy in pancreatic cancer.

Project description:Radiation therapy induces immunogenic cell death in cancer cells, whereby released endogenous adjuvants are sensed by immune cells to direct adaptive immune responses. TLRs expressed on several immune subtypes recognize innate adjuvants to direct downstream inflammatory responses in part via the adapter protein MyD88. We generated Myd88 conditional knockout mice to interrogate its contribution to the immune response to radiation therapy in distinct immune populations in pancreatic cancer. Surprisingly, Myd88 deletion in Itgax (CD11c)-expressing dendritic cells had little discernable effects on response to RT in pancreatic cancer and elicited normal T cell responses using a prime/boost vaccination strategy. Myd88 deletion in Lck-expressing T cells resulted in similar or worsened responses to radiation therapy compared to wild-type mice and lacked antigen-specific CD8+ T cell responses from vaccination, similar to observations in Myd88-/- mice. Lyz2-specific loss of Myd88 in myeloid populations rendered tumors more susceptible to radiation therapy and elicited normal CD8+ T cell responses to vaccination. scRNAseq in Lyz2-Cre/Myd88fl/fl mice revealed gene signatures in macrophages and monocytes indicative of enhanced type I and II interferon responses, and improved responses to RT were dependent on CD8+ T cells and IFNAR1. Together, these data implicate MyD88 signaling in myeloid cells as a critical source of immunosuppression that hinders adaptive immune tumor control following radiation therapy.

| S-EPMC10224952 | biostudies-literature

Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-28 | GSE176015 | GEO

CD8 T cells isolated from treated mice

Project description:CD8 T cells isolated from blood of mice treated with radiation therapy and immunotherapy

2024-06-20 | PXD043110 | JPOST Repository

Effect of radiation therapy

Project description:Effect of radiation therapy

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Ad-MyD88 infected MEFs: Control vs. Ad-MyD88 infected

Project description:Transcriptional profiling of Murine Embryonic Fibroblasts (MEFs) infected with Ad-MyD88 vs. Ad-GFP or mock infected. Three-condition experiment, Ad-MyD88 vs. Ad-GFP vs. Mock infected cells. Biological replicates: 3 Ad-MyD88, 3 Ad-GFP, 3 mock, independently grown and harvested. One replicate per array.

2010-01-28 | E-GEOD-18957 | biostudies-arrayexpress

Ad-MyD88 infected bmDCs: Control vs. Ad-MyD88 infected

Project description:Transcriptional profiling of Bone-Marrow derived mouse Dendritic Cells (bmDCs) infected with Ad-MyD88 vs. Ad-GFP or mock infected Three-condition experiment, Ad-MyD88 vs. Ad-GFP vs. Mock infected cells. Biological replicates: 3 Ad-MyD88, 3 Ad-GFP, 3 mock, independently grown and harvested. One replicate per array.

2010-10-08 | E-GEOD-19006 | biostudies-arrayexpress

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