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

Marion Dajon, Kristina Iribarren, Florent Petitprez, Solenne Marmier, Audrey Lupo, Mélanie Gillard, Hanane Ouakrim, Navas Victor, Di Bartolo Vincenzo, Pierre Emmanuel Joubert, Oliver Kepp, Guido Kroemer, Marco Alifano, Diane Damotte, Isabelle Cremer

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    36 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Article numbere1505174
    JournalOncoImmunology
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 2 Jan 2019

    Keywords

    • EMT
    • MDSC
    • TLR7
    • lung adenocarcinoma
    • metastasis

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