Pascual-García, MónicaBonfill-Teixidor, EsterPlanas-Rigol, EsterRubio-Perez, CarlotaIurlaro, RaffaellaArias, AlexandraCuartas, IsabelSala-Hojman, AdaEscudero, LauraMartínez-Ricarte, FranciscoHuber-Ruano, IsabelNuciforo, PaoloPedrosa, LeireMarques, CarolinaBraña, IreneGarralda, ElenaVieito, MaríaSquatrito, MassimoPineda, EstelaGraus, FrancescEspejo, CarmenSahuquillo, JuanTabernero, JosepSeoane, Joan2019-09-102019-09-102019-06-11Nat Commun. 2019 ;10(1):2416.2041-1723http://hdl.handle.net/20.500.12105/8322Cancer 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.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/AnimalsAntibodies, NeutralizingCD8-Positive T-LymphocytesChemokine CCL2Chemokine CXCL9Epigenesis, GeneticHumansImmunologic MemoryLeukemia Inhibitory FactorLymphocytes, Tumor-InfiltratingMacrophagesMice, Inbred C57BLMice, SCIDNeoplasm TransplantationNeoplasmsProgrammed Cell Death 1 ReceptorTumor MicroenvironmentAtribución-NoComercial-CompartirIgual 4.0 Internacional31186412101241610.1038/s41467-019-10369-92041-1723Nature communicationsopen access