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Página principal > Artículos > Artículos publicados > LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+ T cell tumor-infiltration impairing anti-PD1 therapy |
Fecha: | 2019 |
Resumen: | 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. |
Ayudas: | European Commission 205819 Instituto de Salud Carlos III PI16/01278 Instituto de Salud Carlos III RTC-2015-3771-1 |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | 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 |
Publicado en: | Nature communications, Vol. 10 Núm. 1 (january 2019) , p. 2416, ISSN 2041-1723 |
11 p, 3.2 MB |