Please use this identifier to cite or link to this item: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
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 CNIO | Pineda, Estela | Graus, Francesc | Espejo, Carmen | Sahuquillo, Juan | Tabernero, Josep | Seoane, Joan
Nat Commun. 2019 ;10(1):2416.
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.
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
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