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Título:
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LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy
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Autor/a:
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Pascual García, Mónica; Bonfill Teixidor, Ester; Planas Rigol, Ester; Rubio-Perez, Carlota; Iurlaro, Raffaella; Arias Piñeiro, Alexandra; Cuartas Maza, Ma Isabel; Sala Hojman, Ada; Escudero Monreal, Laura; Martínez Ricarte, Francisco Ramón; Huber Ruano, Isabel; Nuciforo, Paolo Giovanni; Braña Garcia, Irene; Garralda Cabanas, Elena; Vieito Villar, Maria; Espejo Ruiz, Carmen; Sahuquillo Barris, Joan; Tabernero Caturla, Josep; Seoane Suarez, Joan
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Otros autores:
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Institut Català de la Salut; [Pascual-García M, Bonfill-Teixidor E] Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. Hospital Universitari Vall d'Hebron, Barcelona, Spain. CIBERONC, Madrid, Spain. [Planas-Rigol E, Rubio-Perez C, Iurlaro R, Arias A, Cuartas I, Sala-Hojman A, Escudero L, Huber-Ruano I, Nuciforo P, Braña I, Garralda E, Vieito M] Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. Hospital Universitari Vall d'Hebron, Barcelona, Spain. [Martínez-Ricarte F, Espejo C, Sahuquillo J] Vall d’Hebron Institut de Recerca, Barcelona, Spain. Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. [Tabernero J] Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. Hospital Universitari Vall d'Hebron, Barcelona, Spain. CIBERONC, Madrid, Spain. Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. [Seoane J] Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. Hospital Universitari Vall d'Hebron, Barcelona, Spain. CIBERONC, Madrid, Spain. Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.; Hospital Universitari Vall d'Hebron |
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Abstract:
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Càncer; Macròfags associats al tumor: LIF; CD8 |
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Abstract:
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Cáncer; Macrófagos asociados al tumor; CD8 |
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Abstract:
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Cancer; Tumor-associated macrophages; CD8 |
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Abstract:
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Cancer response to immunotherapy depends on the infiltration of CD8+ T cells and the presence of tumor-associated macrophages within tumors. Still, little is known about the determinants of these factors. We show that LIF assumes a crucial role in the regulation of CD8+ T cell tumor infiltration, while promoting the presence of protumoral tumor-associated macrophages. We observe that the blockade of LIF in tumors expressing high levels of LIF decreases CD206, CD163 and CCL2 and induces CXCL9 expression in tumor-associated macrophages. The blockade of LIF releases the epigenetic silencing of CXCL9 triggering CD8+ T cell tumor infiltration. The combination of LIF neutralizing antibodies with the inhibition of the PD1 immune checkpoint promotes tumor regression, immunological memory and an increase in overall survival. |
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Materia(s):
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-Medicaments antineoplàstics
-Cèl·lules T - Immunologia
-Citocines - Immunologia
-Tumors - Tractament
-DISEASES::Neoplasms
-Other subheadings::Other subheadings::Other subheadings::/drug therapy
-CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Leukemia Inhibitory Factor
-ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD8-Positive T-Lymphocytes
-Other subheadings::Other subheadings::Other subheadings::/immunology
-ENFERMEDADES::Neoplasias
-Otros calificadores::Otros calificadores::Otros calificadores::/tratamiento farmacológico
-COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::péptidos::péptidos y proteínas de señalización intercelular::citocinas::factor inhibidor de la leucemia
-ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD8-positivos
-Otros calificadores::Otros calificadores::Otros calificadores::/inmunología |
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Derechos:
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Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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Tipo de documento:
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Artículo
Artículo - Versión publicada |
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Editor:
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Nature Research
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Compartir:
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