| First Author | Cheng HW | Year | 2018 |
| Journal | J Allergy Clin Immunol | Volume | 142 |
| Issue | 4 | Pages | 1257-1271.e4 |
| PubMed ID | 29391257 | Mgi Jnum | J:337353 |
| Mgi Id | MGI:6757520 | Doi | 10.1016/j.jaci.2017.12.998 |
| Citation | Cheng HW, et al. (2018) CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses. J Allergy Clin Immunol 142(4):1257-1271.e4 |
| abstractText | 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. |
