LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.
Nature
; 562(7728): 605-609, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30333625
ABSTRACT
Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
/
Linfócitos T CD4-Positivos
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Transdução de Sinais
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Receptores de Superfície Celular
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Linfócitos T CD8-Positivos
/
Evasão Tumoral
Limite:
Animals
/
Female
/
Humans
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Male
Idioma:
En
Revista:
Nature
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos