气候变化领域集成服务门户(CCPortal): IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions

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DOI	10.1073/pnas.2020395118
	IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions
	Mucciolo G.; Curcio C.; Roux C.; Li W.Y.; Capello M.; Curto R.; Chiarle R.; Giordano D.; Satolli M.A.; Lawlor R.; Scarpa A.; Lukac P.; Stakheev D.; Provero P.; Vannucci L.; Mak T.W.; Novelli F.; Cappello P.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	A hallmark of cancer, including pancreatic ductal adenocarcinoma (PDA), is a massive stromal and inflammatory reaction. Many efforts have been made to identify the anti- or protumoral role of cytokines and immune subpopulations within the stroma. Here, we investigated the role of interleukin-17A (IL17A) and its effect on tumor fibroblasts and the tumor microenvironment. We used a spontaneous PDA mouse model (KPC) crossed to IL17A knockout mice to show an extensive desmoplastic reaction, without impaired immune infiltration. Macrophages, especially CD80+ and T cells, were more abundant at the earlier time point. In T cells, a decrease in FoxP3+ cells and an increase in CD8+ T cells were observed in KPC/ IL17A−/− mice. Fibroblasts isolated from IL17A+/+ and IL17A−/− KPC mice revealed very different messenger RNA (mRNA) and protein profiles. IL17A−/− fibroblasts displayed the ability to restrain tumor cell invasion by producing factors involved in extracellular matrix remodeling, increasing T cell recruitment, and producing higher levels of cytokines and chemokines favoring T helper 1 cell recruitment and activation and lower levels of those recruiting myeloid/granulocytic immune cells. Single-cell quantitative PCR on isolated fibroblasts confirmed a very divergent profile of IL17A-proficient and -deficient cells. All these features can be ascribed to increased levels of IL17F observed in the sera of IL17A−/− mice, and to the higher expression of its cognate receptor (IL17RC) specifically in IL17A−/− cancer-associated fibroblasts (CAFs). In addition to the known effects on neoplastic cell transformation, the IL17 cytokine family uniquely affects fibroblasts, representing a suitable candidate target for combinatorial immune-based therapies in PDA. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cancer-associated fibroblast; Extracellular matrix; Fibrosis; IL17A; Pancreatic cancer
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180760
作者单位	Laboratory of Tumor Immunology, Center for Experimental Research and Medical Studies, Città della Salute e della Scienza di Torino, University of Torino, Torino, 10126, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, 10126, Italy; Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, United States; Medical Oncology Division, Centro Oncologico Ematologico Subalpino, Città della Salute e della Scienza di Torino, Department of Oncology, University of Torino, Torino, 10126, Italy; Applied Research Center (ARC-NET), University of Verona, Verona, 37134, Italy; Department of Diagnostics and Public Health, University of Verona, Verona, 37134, Italy; Laboratory of Immunotherapy, Instit...
推荐引用方式 GB/T 7714	Mucciolo G.,Curcio C.,Roux C.,et al. IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions[J],2021,118(6).
APA	Mucciolo G..,Curcio C..,Roux C..,Li W.Y..,Capello M..,...&Cappello P..(2021).IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Mucciolo G.,et al."IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).