Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells.
EMT
MDSC
TLR7
lung adenocarcinoma
metastasis
Journal
Oncoimmunology
ISSN: 2162-4011
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
Historique:
received:
29
05
2018
revised:
21
07
2018
accepted:
24
07
2018
entrez:
15
12
2018
pubmed:
14
12
2018
medline:
14
12
2018
Statut:
epublish
Résumé
In non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a receptor for single stranded RNA, is linked to tumor progression and resistance to anticancer chemotherapy. However, the mechanism of this effect has been elusive. Here, using a murine model of lung adenocarcinoma, we demonstrate a key role for TLR7 expressed by malignant (rather than by stromal and immune) cells, in the recruitment of myeloid derived suppressor cells (MDSCs), induced after TLR7 stimulation, resulting in accelerated tumor growth and metastasis. In adenocarcinoma patients, high TLR7 expression on malignant cells was associated with poor clinical outcome, as well as with a gene expression signature linked to aggressiveness and metastastic dissemination with high abundance of mRNA encoding intercellular adhesion molecule 1 (ICAM-1), cytokeratins 7 and 19 (KRT-7 and 19), syndecan 4 (SDC4), and p53. In addition, lung tumors expressing high levels of TLR7 have a phenotype of epithelial mesenchymal transition with high expression of vimentin and low abundance of E-cadherin. These data reveal a crucial role for cancer cell-intrinsic TLR7 expression in lung adenocarcinoma progression.
Identifiants
pubmed: 30546943
doi: 10.1080/2162402X.2018.1505174
pii: 1505174
pmc: PMC6287801
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
e1505174Références
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