Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer [Nanostring]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA734585 | ENA |
REPOSITORIES: ENA
Similar Datasets
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 | GSE176014 | GEO
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
Project description:Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer
| PRJNA734581 | ENA
Project description:Myeloid MyD88 restricts CD8+ T cell response to radiation therapy in pancreatic cancer [sequencing]
| PRJNA734576 | ENA
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
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-08-28 | GSE176015 | GEO
Project description:Allergic asthma is a chronic disease of the airways characterized by eosinophilic and neutrophilic inflammation. MYD88, the adaptor molecule for TLR and IL-1 family member signaling, is required for allergic sensitization through the airway in animal models of allergic asthma. We generated conditionally mutant mice separately lacking Myd88 in airway epithelial cells (ECs) or dendritic cells (DCs) and alveolar macrophages (AMs) to define the contribution of Myd88 expression in each of these cell types. To examine crosstalk from ECs to AMs in vivo, we examined transcriptional profiles from lung AMs sorted following 6h in vivo lung allergic sensitization through the airways from WT MyD88 fx/fx, SPC cre+ MyD88 fx/fx (EC-MYD88 KO), CD11c cre+ MyD88 fx/fx (DC-MYD88 KO), and full MyD88 KO mice. We observed immune-specific transcriptional changes in AMs that were cell-intrinsic as well as resulting from in vivo crosstalk from ECs. We also observed transcriptional (linked data set) and epigenetic changes in chromatin conformation in cDCs by ATAC-seq (linked data set) as well as changes in immune-specific whole lung RNA, sorted EC RNA, and sorted cDC RNA by Nanostring nCounter Immunology Codeset Analysis (additional linked files).
2018-03-10 | GSE79592 | GEO
Project description:Allergic asthma is a chronic disease of the airways characterized by eosinophilic and neutrophilic inflammation. MYD88, the adaptor molecule for TLR and IL-1 family member signaling, is required for allergic sensitization through the airway in animal models of allergic asthma. We generated conditionally mutant mice separately lacking Myd88 in airway epithelial cells (ECs) or dendritic cells (DCs) to define the contribution of Myd88 expression in each of these cell types. To examine crosstalk from ECs to conventional (c)DCs in vivo, we examined immune-specific transcriptional profiles from lung cDCs sorted following 6h in vivo lung allergic sensitization through the airways from WT MyD88 fx/fx, SPC cre+ MyD88 fx/fx (EC-MYD88 KO), CD11c cre+ MyD88 fx/fx (DC-MYD88 KO), and full MyD88 KO mice. We observed immune-specific transcriptional changes in cDCs that were cell-intrinsic as well as resulting from in vivo crosstalk from ECs. We also observed transcriptional (linked data set) and epigenetic changes in chromatin conformation in cDCs by ATAC-seq (linked data set) as well as changes in immune-specific whole lung RNA, sorted EC RNA, and sorted alveolar macrophage (AM) RNA by Nanostring nCounter Immunology Codeset Analysis (additional linked files).
2018-03-10 | GSE79614 | GEO
Project description:Allergic asthma is a chronic disease of the airways characterized by eosinophilic and neutrophilic inflammation. MYD88, the adaptor molecule for TLR and IL-1 family member signaling, is required for allergic sensitization through the airway in animal models of allergic asthma. We generated conditionally mutant mice separately lacking Myd88 in airway epithelial cells (ECs) or dendritic cells (DCs) and alveolar macrophages (AMs) to define the contribution of Myd88 expression in each of these cell types. To examine crosstalk from CD11c-expressing cells to ECs in vivo, we examined immune-specific transcriptional profiles from lung ECs sorted following 2h in vivo lung allergic sensitization through the airways from WT MyD88 fx/fx, SPC cre+ MyD88 fx/fx (EC-MYD88 KO), CD11c cre+ MyD88 fx/fx (DC-MYD88 KO), and full MyD88 KO mice. We observed immune-specific transcriptional changes in ECs that were cell-intrinsic but none resulting from in vivo crosstalk from CD11c-expressing cells. We also observed transcriptional (linked data set) and epigenetic changes in chromatin conformation in cDCs by ATAC-seq (linked data set) as well as changes in immune-specific whole lung RNA, sorted AM RNA, and sorted cDC RNA by Nanostring nCounter Immunology Codeset Analysis (additional linked files).
2018-03-10 | GSE79591 | GEO
Project description:Allergic asthma is a chronic disease of the airways characterized by eosinophilic and neutrophilic inflammation. MYD88, the adaptor molecule for TLR and IL-1 family member signaling, is required for allergic sensitization through the airway in animal models of allergic asthma. We generated conditionally mutant mice separately lacking Myd88 in airway epithelial cells (ECs) or dendritic cells (DCs) and alveolar macrophages (AMs) to define the contribution of Myd88 expression in each of these cell types. To examine crosstalk between ECs and CD11c-expressing cells in vivo, we examined transcriptional profiles from whole lung RNA at baseline, or following 2h or 6h in vivo lung allergic sensitization through the airways from WT MyD88 fx/fx, SPC cre+ MyD88 fx/fx (EC-MYD88 KO), CD11c cre+ MyD88 fx/fx (DC-MYD88 KO), and full MyD88 KO mice. We observed immune-specific transcriptional changes in whole lung RNA that were altered based on EC- or CD11c-specific deletion of MYD88. We also observed transcriptional (linked data set) and epigenetic changes in chromatin conformation in cDCs by ATAC-seq (linked data set) as well as changes in immune-specific sorted EC RNA, sorted AM RNA, and sorted cDC RNA by Nanostring nCounter Immunology Codeset Analysis (additional linked files).
2018-03-10 | GSE79594 | GEO