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Cancer Res. 2014 Sep 15;74(18):5008-18. doi: 10.1158/0008-5472.CAN-13-2698. Epub 2014 Jul 29.

TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical outcomes in non-small cell lung cancer.

Author information

1
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.
2
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.
3
Services d'anatomie-pathologie et de chirurgie thoracique, Hôpital Hôtel Dieu AP-HP, Paris, France.
4
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.
5
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.

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.

PMID:
25074614
DOI:
10.1158/0008-5472.CAN-13-2698
[Indexed for MEDLINE]
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