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oai:repisalud.isciii.es:20.500.12105/83222024-11-29T19:42:31Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Pascual-García, Mónica author Bonfill-Teixidor, Ester author Planas-Rigol, Ester author Rubio-Perez, Carlota author Iurlaro, Raffaella author Arias, Alexandra author Cuartas, Isabel author Sala-Hojman, Ada author Escudero, Laura author Martínez-Ricarte, Francisco author Huber-Ruano, Isabel author Nuciforo, Paolo author Pedrosa, Leire author Marques, Carolina author Braña, Irene author Garralda, Elena author Vieito, María author Squatrito, Massimo author Pineda, Estela author Graus, Francesc author Espejo, Carmen author Sahuquillo, Juan author Tabernero, Josep author Seoane, Joan author 2019-06-11 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. Nat Commun. 2019 ;10(1):2416. 10.1038/s41467-019-10369-9 2041-1723 2041-1723 Nature communications 31186412 http://hdl.handle.net/20.500.12105/8322 LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy