TLR7 Promotes Tumor Progression, Chemotherapy Resistance, and Poor Clinical Outcomes in Non–Small Cell Lung Cancer

Toll-like receptors (TLR) recognize pathogen molecules and danger-associated signals that stimulate inflammatory processes. TLRs have been studied mainly in antigen-presenting cells, where they exert important immune regulatory functions, but they are also expressed by epithelial tumor cells, where...

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Published inCancer research (Chicago, Ill.) Vol. 74; no. 18; pp. 5008 - 5018
Main Authors Chatterjee, Saradiya, Crozet, Lucile, Damotte, Diane, Iribarren, Kristina, Schramm, Catherine, Alifano, Marco, Lupo, Audrey, Cherfils-Vicini, Julien, Goc, Jeremy, Katsahian, Sandrine, Younes, Mohammad, Dieu-Nosjean, Marie Caroline, Fridman, Wolf Herman, Sautès-Fridman, Catherine, Cremer, Isabelle
Format Journal Article
LanguageEnglish
Published United States 15.09.2014
Subjects
Animals
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - metabolism
Cell Line, Tumor
Disease Progression
Female
Guanosine - analogs & derivatives
Guanosine - pharmacology
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Membrane Glycoproteins - agonists
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Signal Transduction
Toll-Like Receptor 7 - agonists
Toll-Like Receptor 7 - metabolism
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Summary:Toll-like receptors (TLR) recognize pathogen molecules and danger-associated signals that stimulate inflammatory processes. TLRs have been studied mainly in antigen-presenting cells, where they exert important immune regulatory functions, but they are also expressed by epithelial tumor cells, where they have been implicated in tumor progression. In this study, we demonstrate that the injection of TLR7 agonist in NOD/SCID mice, in C57BL/6 wild-type, and TLR7-deficient mice grafted with lung adenocarcinoma tumor cells leads to increased tumor progression and chemotherapeutic resistance. In patients with non–small cell lung cancer, expression analyses revealed that high TLR7 expression was strongly associated with resistance to neoadjuvant chemotherapy and poor clinical outcomes. Our findings delineate a crucial role for TLR7 in lung cancer physiopathology. Cancer Res; 74(18); 5008–18. ©2014 AACR.
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ISSN:0008-5472
1538-7445
1538-7445
DOI:10.1158/0008-5472.CAN-13-2698