title: TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical outcomes in non-small cell lung cancer.
abstract: 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.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Saradiya
authors: S
authors: Chatterjee
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Lucile
authors: L
authors: Crozet
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France. Services d'anatomie-pathologie et de chirurgie thoracique, Hôpital Hôtel Dieu AP-HP, Paris, France.
authors: Diane
authors: D
authors: Damotte
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Kristina
authors: K
authors: Iribarren
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Catherine
authors: C
authors: Schramm
authors: Services d'anatomie-pathologie et de chirurgie thoracique, Hôpital Hôtel Dieu AP-HP, Paris, France.
authors: Marco
authors: M
authors: Alifano
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Paris Descartes, UMRS1138, Paris, France. Services d'anatomie-pathologie et de chirurgie thoracique, Hôpital Hôtel Dieu AP-HP, Paris, France.
authors: Audrey
authors: A
authors: Lupo
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Julien
authors: J
authors: Cherfils-Vicini
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Jeremy
authors: J
authors: Goc
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Sandrine
authors: S
authors: Katsahian
authors: Services d'anatomie-pathologie et de chirurgie thoracique, Hôpital Hôtel Dieu AP-HP, Paris, France.
authors: Mohammad
authors: M
authors: Younes
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Marie Caroline
authors: MC
authors: Dieu-Nosjean
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Wolf Herman
authors: WH
authors: Fridman
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France.
authors: Catherine
authors: C
authors: Sautès-Fridman
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers, Paris, France. Université Pierre et Marie Curie-Paris 6, UMRS1138, Paris, France. Université Paris Descartes, UMRS1138, Paris, France. isabelle.cremer@crc.jussieu.fr.
authors: Isabelle
authors: I
authors: Cremer
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000819:agonists / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; C495348:TLR7 protein, human; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D006151:Guanosine; C068562:loxoribine