Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells

OncoImmunology

卷:8

Marco Alifano¹  Marion Dajon²  Pierre Emmanuel Joubert²  Florent Petitprez²  Audrey Lupo²  Oliver Kepp²  Kristina Iribarren²  Mélanie Gillard²  Isabelle Cremer²  Diane Damotte²  Solenne Marmier²  Hanane Ouakrim²  Guido Kroemer²  Navas Victor³  Di Bartolo Vincenzo³ 

[1] Departments of Pathology and Thoracic Surgery, Hospital Cochin AP-HP;

[2] Institut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers;

[3] Unité de de Biologie Cellulaire des Lymphocytes INSERM U1221, Institut Pasteur;

关键词: tlr7;    lung adenocarcinoma;    metastasis;    emt;    mdsc;   

DOI  :  10.1080/2162402X.2018.1505174

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown