Ontology type: schema:ScholarlyArticle Open Access: True
2019-12
AUTHORSElena E. Tchekneva, Mounika U.L. Goruganthu, Roman V. Uzhachenko, Portia L. Thomas, Anneliese Antonucci, Irina Chekneva, Michael Koenig, Longzhu Piao, Anwari Akhter, Maria Teresa P. de Aquino, Parvathi Ranganathan, Nicholas Long, Thomas Magliery, Anna Valujskikh, Jason V. Evans, Rajeswara R. Arasada, Pierre P. Massion, David P. Carbone, Anil Shanker, Mikhail M. Dikov
ABSTRACTBACKGROUND: Notch intercellular communication instructs tissue-specific T-cell development and function. In this study, we explored the roles of dendritic cell (DC)-expressed Notch ligands in the regulation of T-cell effector function. METHODS: We generated mice with CD11c lineage-specific deletion of Notch Delta-like ligand (Dll)1 and Jagged (Jag)2. Using these genetically-ablated mice and engineered pharmacological Notch ligand constructs, the roles of various Delta-like and Jagged ligands in the regulation of T-cell-mediated immunity were investigated. We assessed tumor growth, mouse survival, cytokine production, immunophenotyping of myeloid and lymphoid populations infiltrating the tumors, expression of checkpoint molecules and T-cell function in the experimental settings of murine lung and pancreatic tumors and cardiac allograft rejection. Correlative studies were also performed for the expression of NOTCH ligands, NOTCH receptors and PD-1 on various subsets of myeloid and lymphoid cells in tumor-infiltrating immune cells analyzed from primary human lung cancers. RESULTS: Mice with CD11c lineage-specific deletion of Notch ligand gene Dll1, but not Jag2, exhibited accelerated growth of lung and pancreatic tumors concomitant with decreased antigen-specific CD8+T-cell functions and effector-memory (Tem) differentiation. Increased IL-4 but decreased IFN-γ production and elevated populations of T-regulatory and myeloid-derived suppressor cells were observed in Dll1-ablated mice. Multivalent clustered DLL1-triggered Notch signaling overcame DC Dll1 deficiency and improved anti-tumor T-cell responses, whereas the pharmacological interference by monomeric soluble DLL1 construct suppressed the rejection of mouse tumors and cardiac allograft. Moreover, monomeric soluble JAG1 treatment reduced T-regulatory cells and improved anti-tumor immune responses by decreasing the expression of PD-1 on CD8+Tem cells. A significant correlation was observed between DC-expressed Jagged and Delta-like ligands with Tem-expressed PD-1 and Notch receptors, respectively, in human lung tumor-infiltrates. CONCLUSION: Our data show the importance of specific expression of Notch ligands on DCs in the regulation of T-cell effector function. Thus, strategies incorporating selectively engineered Notch ligands could provide a novel approach of therapeutics for modulating immunity in various immunosuppressive conditions including cancer. More... »
PAGES95
http://scigraph.springernature.com/pub.10.1186/s40425-019-0566-4
DOIhttp://dx.doi.org/10.1186/s40425-019-0566-4
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1113179522
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/30940183
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Immunology",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Tchekneva",
"givenName": "Elena E.",
"type": "Person"
},
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Goruganthu",
"givenName": "Mounika U.L.",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Meharry Medical College",
"id": "https://www.grid.ac/institutes/grid.259870.1",
"name": [
"Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College School of Medicine, 2005 Harold D. West Basic Sciences Building, 1023 21st Ave N, 37208, Nashville, TN, USA"
],
"type": "Organization"
},
"familyName": "Uzhachenko",
"givenName": "Roman V.",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Meharry Medical College",
"id": "https://www.grid.ac/institutes/grid.259870.1",
"name": [
"Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College School of Medicine, 2005 Harold D. West Basic Sciences Building, 1023 21st Ave N, 37208, Nashville, TN, USA",
"Department of Microbiology, Immunology and Physiology, Meharry Medical College School of Medicine, Nashville, USA",
"School of Graduate Studies and Research, Meharry Medical College, Nashville, TN, USA"
],
"type": "Organization"
},
"familyName": "Thomas",
"givenName": "Portia L.",
"type": "Person"
},
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Antonucci",
"givenName": "Anneliese",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Sechenov University",
"id": "https://www.grid.ac/institutes/grid.448878.f",
"name": [
"Sechenov First Moscow State Medical University, Moscow, Russia"
],
"type": "Organization"
},
"familyName": "Chekneva",
"givenName": "Irina",
"type": "Person"
},
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Koenig",
"givenName": "Michael",
"type": "Person"
},
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Piao",
"givenName": "Longzhu",
"type": "Person"
},
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Akhter",
"givenName": "Anwari",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Meharry Medical College",
"id": "https://www.grid.ac/institutes/grid.259870.1",
"name": [
"Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College School of Medicine, 2005 Harold D. West Basic Sciences Building, 1023 21st Ave N, 37208, Nashville, TN, USA"
],
"type": "Organization"
},
"familyName": "de Aquino",
"givenName": "Maria Teresa P.",
"type": "Person"
},
{
"affiliation": {
"alternateName": "The Ohio State University Wexner Medical Center",
"id": "https://www.grid.ac/institutes/grid.412332.5",
"name": [
"Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Ranganathan",
"givenName": "Parvathi",
"type": "Person"
},
{
"affiliation": {
"alternateName": "The Ohio State University",
"id": "https://www.grid.ac/institutes/grid.261331.4",
"name": [
"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Long",
"givenName": "Nicholas",
"type": "Person"
},
{
"affiliation": {
"alternateName": "The Ohio State University",
"id": "https://www.grid.ac/institutes/grid.261331.4",
"name": [
"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Magliery",
"givenName": "Thomas",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Cleveland Clinic",
"id": "https://www.grid.ac/institutes/grid.239578.2",
"name": [
"Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA"
],
"type": "Organization"
},
"familyName": "Valujskikh",
"givenName": "Anna",
"type": "Person"
},
{
"affiliation": {
"alternateName": "West Virginia University",
"id": "https://www.grid.ac/institutes/grid.268154.c",
"name": [
"Department of Pathology, West Virginia University, Morgantown, WV, USA"
],
"type": "Organization"
},
"familyName": "Evans",
"givenName": "Jason V.",
"type": "Person"
},
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Arasada",
"givenName": "Rajeswara R.",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Vanderbilt University",
"id": "https://www.grid.ac/institutes/grid.152326.1",
"name": [
"Department of Medicine, Vanderbilt University, Nashville, TN, USA"
],
"type": "Organization"
},
"familyName": "Massion",
"givenName": "Pierre P.",
"type": "Person"
},
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Carbone",
"givenName": "David P.",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Vanderbilt University",
"id": "https://www.grid.ac/institutes/grid.152326.1",
"name": [
"Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College School of Medicine, 2005 Harold D. West Basic Sciences Building, 1023 21st Ave N, 37208, Nashville, TN, USA",
"School of Graduate Studies and Research, Meharry Medical College, Nashville, TN, USA",
"Host\u2013Tumor Interactions Research Program, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, TN, USA",
"Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University, Nashville, TN, USA"
],
"type": "Organization"
},
"familyName": "Shanker",
"givenName": "Anil",
"type": "Person"
},
{
"affiliation": {
"name": [
"Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, 460 W 12th Ave, 484 BRT, 43210, Columbus, OH, USA"
],
"type": "Organization"
},
"familyName": "Dikov",
"givenName": "Mikhail M.",
"type": "Person"
}
],
"citation": [
{
"id": "https://doi.org/10.4049/jimmunol.0804322",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1003714550"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/eji.201243151",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007764265"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0092-8674(04)00451-9",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007766223"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.1300643",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011495390"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1186/s13287-015-0021-5",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011679692",
"https://doi.org/10.1186/s13287-015-0021-5"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1186/s13287-015-0021-5",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1011679692",
"https://doi.org/10.1186/s13287-015-0021-5"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0070-2153(10)92003-6",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1012465515"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nri2488",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016454220",
"https://doi.org/10.1038/nri2488"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.1003658",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1017012000"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s1074-7613(03)00270-x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018460916"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s1074-7613(03)00270-x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018460916"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1128/mbio.00436-16",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018931230"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-14-1154",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1019133416"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.immuni.2014.12.027",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020038406"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.immuni.2014.12.027",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020038406"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1111/j.1365-3083.2011.02541.x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020320276"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.cell.2009.03.045",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1021056409"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.2217/imt.11.126",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1021424075"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2008-03-144980",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1022884674"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nri3445",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1025045334",
"https://doi.org/10.1038/nri3445"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.0903152",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026926300"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1242/dev.02284",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1028718626"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.immuni.2007.05.021",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029183667"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ni1075",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029743779",
"https://doi.org/10.1038/ni1075"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ni1075",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029743779",
"https://doi.org/10.1038/ni1075"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.immuni.2013.07.006",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1031119344"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.jaci.2008.01.004",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1031355511"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/dvg.20626",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1034217129"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/dvg.20626",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1034217129"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/2326-6066.cir-14-0021",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1035561972"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature04753",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037247321",
"https://doi.org/10.1038/nature04753"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature04753",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037247321",
"https://doi.org/10.1038/nature04753"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/eji.200636325",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1042505796"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1677/joe-07-0242",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1047430342"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2008-02-136325",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048185901"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1111/j.1365-3083.2012.02673.x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049005954"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-10-4366",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049272744"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/icb.2012.53",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049831238",
"https://doi.org/10.1038/icb.2012.53"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.18632/oncotarget.5857",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1051874810"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1084/jem.20062305",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1053213314"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1136/gutjnl-2016-311585",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1062813718"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.171.6.3019",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1075344874"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.172.9.5456",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1076828414"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.173.12.7109",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1076976732"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.178.2.858",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1077343853"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.180.3.1655",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1077593517"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.180.12.7931",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1077656163"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.0903661",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1078138582"
],
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1083245791",
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ncomms15338",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1085462858",
"https://doi.org/10.1038/ncomms15338"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1136/esmoopen-2017-000213",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1090338292"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-17-0357",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1091691930"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4049/jimmunol.1700070",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1100451415"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3389/fimmu.2018.01649",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1105604383"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.2217/imt-2018-0135",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1110472202"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.2217/imt-2018-0135",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1110472202"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.2217/imt-2018-0135",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1110472202"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.2217/imt-2018-0135",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1110472202"
],
"type": "CreativeWork"
}
],
"datePublished": "2019-12",
"datePublishedReg": "2019-12-01",
"description": "BACKGROUND: Notch intercellular communication instructs tissue-specific T-cell development and function. In this study, we explored the roles of dendritic cell (DC)-expressed Notch ligands in the regulation of T-cell effector function.\nMETHODS: We generated mice with CD11c lineage-specific deletion of Notch Delta-like ligand (Dll)1 and Jagged (Jag)2. Using these genetically-ablated mice and engineered pharmacological Notch ligand constructs, the roles of various Delta-like and Jagged ligands in the regulation of T-cell-mediated immunity were investigated. We assessed tumor growth, mouse survival, cytokine production, immunophenotyping of myeloid and lymphoid populations infiltrating the tumors, expression of checkpoint molecules and T-cell function in the experimental settings of murine lung and pancreatic tumors and cardiac allograft rejection. Correlative studies were also performed for the expression of NOTCH ligands, NOTCH receptors and PD-1 on various subsets of myeloid and lymphoid cells in tumor-infiltrating immune cells analyzed from\u00a0primary human lung cancers.\nRESULTS: Mice with CD11c lineage-specific deletion of Notch ligand gene\u00a0Dll1, but not Jag2, exhibited accelerated growth of lung and pancreatic tumors concomitant with decreased antigen-specific CD8+T-cell functions and effector-memory (Tem) differentiation. Increased IL-4 but decreased IFN-\u03b3 production and elevated populations of T-regulatory and myeloid-derived suppressor cells were observed\u00a0in Dll1-ablated mice. Multivalent clustered DLL1-triggered Notch signaling overcame DC Dll1 deficiency and improved anti-tumor T-cell responses, whereas the pharmacological interference by monomeric soluble DLL1 construct suppressed the rejection of mouse tumors and cardiac allograft. Moreover, monomeric soluble JAG1 treatment reduced T-regulatory cells and improved anti-tumor immune responses by decreasing the expression of PD-1 on CD8+Tem cells. A significant correlation was observed between DC-expressed Jagged and Delta-like ligands with Tem-expressed PD-1 and Notch receptors, respectively, in human lung tumor-infiltrates.\nCONCLUSION: Our data show the importance of specific expression of Notch ligands on DCs in the regulation of T-cell effector function. Thus, strategies incorporating selectively engineered Notch ligands could provide a novel approach of therapeutics for modulating immunity in various immunosuppressive conditions including cancer.",
"genre": "research_article",
"id": "sg:pub.10.1186/s40425-019-0566-4",
"inLanguage": [
"en"
],
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.2482322",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.4455975",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2679690",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2480391",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2699420",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2699137",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1049249",
"issn": [
"2051-1426"
],
"name": "Journal for ImmunoTherapy of Cancer",
"type": "Periodical"
},
{
"issueNumber": "1",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "7"
}
],
"name": "Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T cell immunity",
"pagination": "95",
"productId": [
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1186/s40425-019-0566-4"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1113179522"
]
},
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"1783ae52ad6334788be16a35c48ceac19b324aa90559885637ad8f276f4b446b"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"101620585"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"30940183"
]
}
],
"sameAs": [
"https://doi.org/10.1186/s40425-019-0566-4",
"https://app.dimensions.ai/details/publication/pub.1113179522"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-16T06:21",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000377_0000000377/records_106807_00000002.jsonl",
"type": "ScholarlyArticle",
"url": "https://link.springer.com/10.1186%2Fs40425-019-0566-4"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s40425-019-0566-4'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s40425-019-0566-4'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s40425-019-0566-4'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s40425-019-0566-4'
This table displays all metadata directly associated to this object as RDF triples.
388 TRIPLES
21 PREDICATES
78 URIs
21 LITERALS
9 BLANK NODES