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The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2.
Hartwig, Torsten; Montinaro, Antonella; von Karstedt, Silvia; Sevko, Alexandra; Surinova, Silvia; Chakravarthy, Ankur; Taraborrelli, Lucia; Draber, Peter; Lafont, Elodie; Arce Vargas, Frederick; El-Bahrawy, Mona A; Quezada, Sergio A; Walczak, Henning.
Affiliation
  • Hartwig T; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Montinaro A; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • von Karstedt S; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Sevko A; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Surinova S; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Chakravarthy A; Department of Oncology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Taraborrelli L; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Draber P; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Lafont E; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Arce Vargas F; Cancer Immunology Unit, Department of Haematology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • El-Bahrawy MA; Department of Histopathology, Imperial College London, London W12 0NN, UK.
  • Quezada SA; Cancer Immunology Unit, Department of Haematology, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  • Walczak H; Centre for Cell Death, Cancer, and Inflammation, Department of Cancer Biology, UCL Cancer Institute, University College London, London WC1E 6DD, UK. Electronic address: h.walczak@ucl.ac.uk.
Mol Cell ; 65(4): 730-742.e5, 2017 Feb 16.
Article in En | MEDLINE | ID: mdl-28212753
ABSTRACT
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant cancer cells is FADD dependent and identify the TRAIL-induced secretome to drive monocyte polarization to myeloid-derived suppressor cells (MDSCs) and M2-like macrophages. TRAIL-R suppression in tumor cells impaired CCL2 production and diminished both lung MDSC presence and tumor growth. In accordance, the receptor of CCL2, CCR2, is required to facilitate increased MDSC presence and tumor growth. Finally, TRAIL and CCL2 are co-regulated with MDSC/M2 markers in lung adenocarcinoma patients. Collectively, endogenous TRAIL/TRAIL-R-mediated CCL2 secretion promotes accumulation of tumor-supportive immune cells in the cancer microenvironment, thereby revealing a tumor-supportive immune-modulatory role of the TRAIL/TRAIL-R system in cancer biology.
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Full text: 1 Database: MEDLINE Main subject: Adenocarcinoma / Cytokines / Carcinoma, Non-Small-Cell Lung / TNF-Related Apoptosis-Inducing Ligand / Receptors, CCR2 / Tumor Microenvironment / Lung Neoplasms / Macrophages Type of study: Prognostic_studies Language: En Year: 2017 Type: Article
Fulltext
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Full text: 1 Database: MEDLINE Main subject: Adenocarcinoma / Cytokines / Carcinoma, Non-Small-Cell Lung / TNF-Related Apoptosis-Inducing Ligand / Receptors, CCR2 / Tumor Microenvironment / Lung Neoplasms / Macrophages Type of study: Prognostic_studies Language: En Year: 2017 Type: Article