LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy

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, wh...

Descripción completa

Detalles Bibliográficos
Autores: Pascual-García, Mónica, Bonfill-Teixidor, Ester, Planas-Rigol, Ester, Rubio-Perez, Carlota, Iurlaro, Raffaella, Arias, Alexandra, Cuartas, Isabel, Sala-Hojman, Ada, Escudero, Laura, Martínez-Ricarte, Francisco, Huber-Ruano, Isabel, Nuciforo, Paolo, Pedrosa, Leire, Marques, Carolina, Braña, Irene, Garralda, Elena, Vieito, María, Squatrito, Massimo, Pineda, Estela, Graus, Francesc, Espejo, Carmen, Sahuquillo, Juan, Tabernero, Josep, Seoane, Joan
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/8322
Acceso en línea:http://hdl.handle.net/20.500.12105/8322
Access Level:acceso abierto
Palabra clave:Animals
Antibodies, Neutralizing
CD8-Positive T-Lymphocytes
Chemokine CCL2
Chemokine CXCL9
Epigenesis, Genetic
Humans
Immunologic Memory
Leukemia Inhibitory Factor
Lymphocytes, Tumor-Infiltrating
Macrophages
Mice, Inbred C57BL
Mice, SCID
Neoplasm Transplantation
Neoplasms
Programmed Cell Death 1 Receptor
Tumor Microenvironment
Descripción
Sumario: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.

Similares en LA Referencia