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

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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.

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Cheng, H. W., Onder, L., Cupovic, J., Boesch, M., Novkovic, M., Pikor, N., … Ludewig, B. (2018). CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses. Journal of Allergy and Clinical Immunology, 142(4), 1257-1271.e4. https://doi.org/10.1016/j.jaci.2017.12.998

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