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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:142

Article

Cheng, Hung-Wei¹  Onder, Lucas¹  Cupovic, Jovana¹  Boesch, Maximilian¹  Novkovic, Mario¹  Pikor, Natalia¹  Tarantino, Ignazio²  Rodriguez, Regulo³  Schneider, Tino⁴  Jochum, Wolfram³  Brutsche, Martin⁴  Ludewig, Burkhard¹ 

[1] Kantonsspital St Gallen, Inst Immunobiol, CH-9007 St Gallen, Switzerland

[2] Kantonsspital St Gallen, Clin Visceral Surg, St Gallen, Switzerland

[3] Kantonsspital St Gallen, Inst Pathol, St Gallen, Switzerland

[4] Kantonsspital St Gallen, Div Pneumol, St Gallen, Switzerland

关键词: Lung inflammation;    lung adenocarcinoma;    fibroblastic reticular cells;    tumor microenvironment;   

DOI  :  10.1016/j.jaci.2017.12.998

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free