| http://purl.uniprot.org/citations/37819238 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37819238 | http://www.w3.org/2000/01/rdf-schema#comment | "The immune suppressive microenvironment is a major culprit for difficult-to-treat solid cancers. Particularly, inhibitory tumor-associated macrophages (TAM) define the resistant nature of the tumor milieu. To define tumor-enabling mechanisms of TAMs, we analyzed molecular clinical datasets correlating cell surface receptors with the TAM infiltrate. Though P-selectin glycoprotein ligand-1 (PSGL-1) is found on other immune cells and functions as an adhesion molecule, PSGL-1 is highly expressed on TAMs across multiple tumor types. siRNA-mediated knockdown and antibody-mediated inhibition revealed a role for PSGL-1 in maintaining an immune suppressed macrophage state. PSGL-1 knockdown or inhibition enhanced proinflammatory mediator release across assays and donors in vitro. In several syngeneic mouse models, PSGL-1 blockade alone and in combination with PD-1 blockade reduced tumor growth. Using a humanized tumor model, we observed the proinflammatory TAM switch following treatment with an anti-PSGL-1 antibody. In ex vivo patient-derived tumor cultures, a PSGL-1 blocking antibody increased expression of macrophage-derived proinflammatory cytokines, as well as IFNγ, indicative of T-cell activation. Our data demonstrate that PSGL-1 blockade reprograms TAMs, offering a new therapeutic avenue to patients not responding to T-cell immunotherapies, as well as patients with tumors devoid of T cells.SignificanceThis work is a significant and actionable advance, as it offers a novel approach to treating patients with cancer who do not respond to T-cell checkpoint inhibitors, as well as to patients with tumors lacking T-cell infiltration. We expect that this mechanism will be applicable in multiple indications characterized by infiltration of TAMs."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.org/dc/terms/identifier | "doi:10.1158/2767-9764.crc-22-0513"xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Nguyen P.A."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Rooney K."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Vollmann E.H."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Novobrantseva T.I."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Ries C."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Zafari M."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Feldman I."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Kauffman K."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Brehm M."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Manfra D."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Nowakowska D."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "O'Nuallain B."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Culyba E.K."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Phennicie R."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Wahle J."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Basinski S."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Komoroski V."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/author | "Sazinsky S."xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/name | "Cancer Res Commun"xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/pages | "2182-2194"xsd:string |
| http://purl.uniprot.org/citations/37819238 | http://purl.uniprot.org/core/title | "PSGL-1 Blockade Induces Classical Activation of Human Tumor-associated Macrophages."xsd:string |