CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses - 05/10/18
Abstract |
Background |
A particular characteristic of non–small cell lung cancer is the composition of the tumor microenvironment with a very high proportion of fibroblastic stromal cells (FSCs).
Objective |
Lapses in our basic knowledge of fibroblast phenotype and function in the tumor microenvironment make it difficult to define whether FSC subsets exist that exhibit either tumor-promoting or tumor-suppressive properties.
Methods |
We used gene expression profiling of lung versus tumor FSCs from patients with non–small cell lung cancer. Moreover, CCL19-expressing FSCs were studied in transgenic mouse models by using a lung cancer metastasis model.
Results |
CCL19 mRNA expression in human tumor FSCs correlates with immune cell infiltration and intratumoral accumulation of CD8+ T cells. Mechanistic dissection in murine lung carcinoma models revealed that CCL19-expressing FSCs form perivascular niches to promote accumulation of CD8+ T cells in the tumor. Targeted ablation of CCL19-expressing tumor FSCs reduced immune cell recruitment and resulted in unleashed tumor growth.
Conclusion |
These data suggest that a distinct population of CCL19-producing FSCs fosters the development of an immune-stimulating intratumoral niche for immune cells to control cancer growth.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Lung inflammation, lung adenocarcinoma, fibroblastic reticular cells, tumor microenvironment
Abbreviations used : ADC, APC, CAF, DC, DT, ECM, EpCAM, EYFP, FC, FITC, FRC, FSC, ICAM-1, LLC, LTβR, NSCLC, PE, Rag, SCC, SMA, Tbp, TLS, TME, VCAM-1
Plan
| Supported by the Swiss National Science Foundation (146133 to B.L.), the Swiss Cancer League (KLS-2880-02-2012 to B.L. and M.B.), the Cancer League of Eastern Switzerland (to B.L. and M.B.), and the Wilhelm Sander Foundation (2011.080.1 to B.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 4
P. 1257 - octobre 2018 Retour au numéro
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