CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T cell responses

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Hung-Wei Cheng, Lucas Onder, Jovana Cupovic, Maximilian Boesch, Mario Novkovic, Natalia Pikor, Ignazio Tarantino, Regulo Rodriguez, Tino Schneider, Wolfram Jochum, Martin Brutsche, Burkhard Ludewig
BackgroundA particular characteristic of non-small cell lung cancer (NSCLC) is the composition of the tumor microenvironment with a very high proportion of fibroblastic stromal cells (FSC).ObjectiveLapses 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.MethodsWe employed gene expression profiling of lung versus tumor FSC from NSCLC patients. Moreover, CCL19-expressing FSCs were studied in transgenic mouse models utilizing a lung cancer metastasis model.ResultsCCL19 mRNA expression in human tumor FSC correlates with immune cell infiltration and intratumoral accumulation of CD8⁺ T cells. Mechanistic dissection in murine lung carcinoma models revealed that CCL19-expressing FSC form perivascular niches to promote accumulation of CD8⁺ T cells in the tumor. Targeted ablation of CCL19-expressing tumor FSC reduced immune cell recruitment and resulted in unleashed tumor growth.ConclusionThese data suggest that a distinct population of CCL19-producing FSC fosters the development of an immune-stimulating intratumoral niche for immune cells to control cancer growth.

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