Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells
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 adenocarcinom...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1505174 |
| _version_ | 1818295137513504768 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Marion Dajon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T03:42:52Z |
| format | Article |
| id | doaj.art-3d8711a3d69047dc912aa59845b4beaa |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-13T03:42:52Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-3d8711a3d69047dc912aa59845b4beaa2022-12-22T00:00:53ZengTaylor & Francis GroupOncoImmunology2162-402X2019-01-018110.1080/2162402X.2018.15051741505174Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cellsMarion Dajon0Kristina Iribarren1Florent Petitprez2Solenne Marmier3Audrey Lupo4Mélanie Gillard5Hanane Ouakrim6Navas Victor7Di Bartolo Vincenzo8Pierre Emmanuel Joubert9Oliver Kepp10Guido Kroemer11Marco Alifano12Diane Damotte13Isabelle Cremer14Institut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersUnité de de Biologie Cellulaire des Lymphocytes INSERM U1221, Institut PasteurUnité de de Biologie Cellulaire des Lymphocytes INSERM U1221, Institut PasteurInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersDepartments of Pathology and Thoracic Surgery, Hospital Cochin AP-HPInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersInstitut National de la Santé et de la Recherche Medicale (INSERM), UMRS1138, Centre de Recherche des CordeliersIn 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.http://dx.doi.org/10.1080/2162402X.2018.1505174tlr7lung adenocarcinomametastasisemtmdsc |
| spellingShingle | 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 Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells OncoImmunology tlr7 lung adenocarcinoma metastasis emt mdsc |
| title | Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells |
| title_full | Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells |
| title_fullStr | Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells |
| title_full_unstemmed | Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells |
| title_short | Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells |
| title_sort | toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells |
| topic | tlr7 lung adenocarcinoma metastasis emt mdsc |
| url | http://dx.doi.org/10.1080/2162402X.2018.1505174 |
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