Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Cancer Immunol Immunother. 2019 Jan;68(1):109-120. doi: 10.1007/s00262-018-2259-0. Epub 2018 Oct 12.

Association of IL-36γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer.

Weinstein AM1,2,3,4,5, Giraldo NA6,7,8,9, Petitprez F6,7,8,10, Julie C11,12, Lacroix L6,7,8, Peschaud F11,12, Emile JF11,12, Marisa L10, Fridman WH6,7,8, Storkus WJ13,14,15,16, Sautès-Fridman C6,7,8.

Author information

1
INSERM, UMR_S 1138, Cordeliers Research Center, Team "Cancer, Immune Control and Escape", 75006, Paris, France. aliyahweinstein@gmail.com.
2
University Paris Descartes, Paris 5, Sorbonne Paris Cite, UMR_S 1138, Centre de Recherche des Cordeliers, 75006, Paris, France. aliyahweinstein@gmail.com.
3
Sorbonne University, UMR_S 1138, Centre de Recherche des Cordeliers, 75006, Paris, France. aliyahweinstein@gmail.com.
4
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA. aliyahweinstein@gmail.com.
5
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA. aliyahweinstein@gmail.com.
6
INSERM, UMR_S 1138, Cordeliers Research Center, Team "Cancer, Immune Control and Escape", 75006, Paris, France.
7
University Paris Descartes, Paris 5, Sorbonne Paris Cite, UMR_S 1138, Centre de Recherche des Cordeliers, 75006, Paris, France.
8
Sorbonne University, UMR_S 1138, Centre de Recherche des Cordeliers, 75006, Paris, France.
9
Pathology Department, Johns Hopkins Hospital, Baltimore, MD, 21287, USA.
10
Programme Cartes d'Identités des Tumeurs, Ligue Nationale contre le Cancer, 75013, Paris, France.
11
Laboratoire d'anatomie pathologique, Hopital Ambroise Paré, AP-HP, Boulogne, France.
12
EA4340, Université de Versailles SQY, Université Paris Saclay, Boulogne, France.
13
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
14
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
15
Department of Pathology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
16
Department of Bioengineering, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.

Abstract

IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36γ 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-36γ 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-36γ 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-36γ expression in this disease. In the colorectal tumor microenvironment, we observed IL-36γ to be predominantly expressed by M1 macrophages and cells of the vasculature, including smooth muscle cells and high endothelial venules. This pattern of IL-36γ 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-36γ in the physiologic immune response to colorectal cancer by sustaining inflammation within the tumor microenvironment.

KEYWORDS:

Colorectal cancer; Interleukin (IL)-36 g; M1 classically activated macrophages; Memory T cells; Tertiary lymphoid structure

PMID:
30315348
DOI:
10.1007/s00262-018-2259-0
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center