The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2
Torsten Hartwig
1
,
Antonella Montinaro
1
,
Silvia Von Karstedt
1
,
Alexandra Sevko
1
,
Silvia Surinova
1
,
Ankur Chakravarthy
2
,
Lucia Taraborrelli
1
,
Peter Draber
1
,
Élodie Lafont
1
,
Frederick Arce Vargas
3
,
Mona El-Bahrawy
4
,
Sergio Quezada
3
,
Henning Walczak
1
Publication type: Journal Article
Publication date: 2017-02-17
scimago Q1
wos Q1
SJR: 9.051
CiteScore: 24.4
Impact factor: 16.6
ISSN: 10972765, 10974164
PubMed ID:
28212753
Molecular Biology
Cell Biology
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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Total citations:
203
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GOST
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Hartwig T. et al. The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2 // Molecular Cell. 2017. Vol. 65. No. 4. pp. 730-74200000.
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Hartwig T., Montinaro A., Von Karstedt S., Sevko A., Surinova S., Chakravarthy A., Taraborrelli L., Draber P., Lafont É., Arce Vargas F., El-Bahrawy M., Quezada S., Walczak H. The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2 // Molecular Cell. 2017. Vol. 65. No. 4. pp. 730-74200000.
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RIS
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TY - JOUR
DO - 10.1016/j.molcel.2017.01.021
UR - https://doi.org/10.1016/j.molcel.2017.01.021
TI - The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2
T2 - Molecular Cell
AU - Hartwig, Torsten
AU - Montinaro, Antonella
AU - Von Karstedt, Silvia
AU - Sevko, Alexandra
AU - Surinova, Silvia
AU - Chakravarthy, Ankur
AU - Taraborrelli, Lucia
AU - Draber, Peter
AU - Lafont, Élodie
AU - Arce Vargas, Frederick
AU - El-Bahrawy, Mona
AU - Quezada, Sergio
AU - Walczak, Henning
PY - 2017
DA - 2017/02/17
PB - Elsevier
SP - 730-74200000
IS - 4
VL - 65
PMID - 28212753
SN - 1097-2765
SN - 1097-4164
ER -
Cite this
BibTex (up to 50 authors)
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@article{2017_Hartwig,
author = {Torsten Hartwig and Antonella Montinaro and Silvia Von Karstedt and Alexandra Sevko and Silvia Surinova and Ankur Chakravarthy and Lucia Taraborrelli and Peter Draber and Élodie Lafont and Frederick Arce Vargas and Mona El-Bahrawy and Sergio Quezada and Henning Walczak},
title = {The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2},
journal = {Molecular Cell},
year = {2017},
volume = {65},
publisher = {Elsevier},
month = {feb},
url = {https://doi.org/10.1016/j.molcel.2017.01.021},
number = {4},
pages = {730--74200000},
doi = {10.1016/j.molcel.2017.01.021}
}
Cite this
MLA
Copy
Hartwig, Torsten, et al. “The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2.” Molecular Cell, vol. 65, no. 4, Feb. 2017, pp. 730-74200000. https://doi.org/10.1016/j.molcel.2017.01.021.