Authors: Mónica Pascual-García, Ester Bonfill-Teixidor, Ester Planas-Rigol, Carlota Rubio-Perez, Raffaella Iurlaro, Alexandra Arias, Isabel Cuartas, Ada Sala-Hojman, Laura Escudero, Francisco Martínez-Ricarte, Isabel Huber-Ruano, Paolo Nuciforo, Leire Pedrosa, Carolina Marques, Irene Braña, Elena Garralda, María Vieito, Massimo Squatrito, Estela Pineda, Francesc Graus, Carmen Espejo, Juan Sahuquillo, Josep Tabernero, Joan Seoane
Published: 2019-06-11
DOI: 10.1038/s41467-019-10369-9
Source: Full article
AbstractCancer 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.