期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 68, 期 1, 页码 109-120出版社
SPRINGER
DOI: 10.1007/s00262-018-2259-0
关键词
Tertiary lymphoid structure; Interleukin (IL)-36g; Colorectal cancer; Memory T cells; M1 classically activated macrophages
资金
- Institut National de la Sante et de la Recherche Medicale
- University Paris-Descartes
- Labex Immuno-Oncology [LAXE62_9UMRS972 FRIDMAN]
- Cancer Research for Personalized Medecine programmes (CARPEM T8)
- Institut du Cancer (INCa) HTE Plan Cancer [C1608DS]
- NIH [RO1 CA169118, RO1 CA204419]
- Chateaubriand Fellowship of the Office for Science and Technology of the Embassy of France in the United States
- CARPEM doctorate fellowship
- University Pierre et Marie Curie
IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36 is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36 controls tertiary lymphoid structure formation and promotes a type-1 immune response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment. Here, we demonstrate that IL-36 plays a similar role in driving a pro-inflammatory phenotype in human colorectal cancer. We analyzed a cohort of 33 primary colorectal carcinoma tumors using imaging, flow cytometry, and transcriptomics to determine the pattern and role of IL-36 expression in this disease. In the colorectal tumor microenvironment, we observed IL-36 to be predominantly expressed by M1 macrophages and cells of the vasculature, including smooth muscle cells and high endothelial venules. This pattern of IL-36 expression is associated with a CD4(+) central memory T cell infiltrate and an increased density of B cells in tertiary lymphoid structures, as well as with markers of fibrosis. Conversely, expression of the antagonist to IL-36 signaling, IL-1F5, was associated with intratumoral expression of checkpoint molecules, including PD-1, PD-L1, and CTLA4, which can suppress the immune response. These data support a role for IL-36 in the physiologic immune response to colorectal cancer by sustaining inflammation within the tumor microenvironment.
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