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<sup>+</sup> 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<sup&...

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Detalhes 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 Ribas, Francesc, Espejo, Carmen, Sahuquillo, Juan, Tabernero Caturla, Josep, Seoane Suárez, Joan
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2019
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/219544
Acesso em linha:https://hdl.handle.net/2445/219544
Access Level:Acceso aberto
Palavra-chave:Macròfags
Càncer
Immunoteràpia
Citocines
Macrophages
Cancer
Immunotheraphy
Cytokines
Descrição
Resumo:Cancer response to immunotherapy depends on the infiltration of CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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.

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