期刊
CELL REPORTS
卷 40, 期 7, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2022.111201
关键词
-
类别
资金
- NIH/National Cancer Institute [R01CA252937, R01CA230275, U01CA196406]
- American Cancer Society [127508-RSG-15-045-01-LIB]
- Leukemia and Lymphoma Society [6551-18]
- UW Trillium Myeloma Fund
- Robert J. Shillman Foundation
- A.G. Leventis, Gerondelis
- Mentzelopoulos Foundations
- NLM [T15LM011271]
The stroma near the tumor edge plays a crucial role in regulating the abundance and activity of cDC1, which in turn affects the T cell inflammatory response in the tumor microenvironment.
Stimulatory type 1 conventional dendritic cells (cDC1s) engage in productive interactions with CD8(+) effectors along tumor-stroma boundaries. The paradoxical accumulation of poised cDC1s within stromal sheets is unlikely to simply reflect passive exclusion from tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling generates developmentally conserved cell fate cues that regulate cDC1 behavior. We find that, in human T cell-inflamed tumors, CD8(+) T cells penetrate tumor nests, whereas cDC1s are confined within adjacent stroma that recurrently displays site-specific proteolysis of the matrix proteoglycan versican (VCAN), an essential organ-sculpting modification in development. VCAN is necessary, and its proteolytic fragment (matrikine) versikine is sufficient for cDC1 accumulation. Versikine does not influence tumor-seeding pre-DC differentiation; rather, it orchestrates a distinctive cDC1 activation program conferring exquisite sensitivity to DNA sensing, supported by atypical innate lymphoid cells. Thus, peritumoral stroma mimicking embryonic provisional matrix remodeling regulates cDC1 abundance and activity to elicit T cell-inflamed tumor microenvironments.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据