Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 1/2019

12.10.2018 | Original Article

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

verfasst von: Aliyah M. Weinstein, Nicolas A. Giraldo, Florent Petitprez, Catherine Julie, Laetitia Lacroix, Frédérique Peschaud, Jean-François Emile, Laetitia Marisa, Wolf H. Fridman, Walter J. Storkus, Catherine Sautès-Fridman

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
3.
Zurück zum Zitat Ribassin-Majed L, Le Teuff G, Hill C (2017) La fréquence des cancers en 2016 et leur évolution. Bull Cancer 104:20–29CrossRefPubMed Ribassin-Majed L, Le Teuff G, Hill C (2017) La fréquence des cancers en 2016 et leur évolution. Bull Cancer 104:20–29CrossRefPubMed
12.
Zurück zum Zitat Penha R, Higgins J, Mutamba S et al (2016) IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose-dependently activated via IL-36β and induces CD4+ lymphocyte proliferation. Cytokine 85:18–25CrossRefPubMed Penha R, Higgins J, Mutamba S et al (2016) IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose-dependently activated via IL-36β and induces CD4+ lymphocyte proliferation. Cytokine 85:18–25CrossRefPubMed
41.
45.
Zurück zum Zitat Wang Z-S, Cong Z-J, Luo Y et al (2014) Decreased expression of interleukin-36α predicts poor prognosis in colorectal cancer patients. Int J Clin Exp Pathol 7:8077–8081PubMedPubMedCentral Wang Z-S, Cong Z-J, Luo Y et al (2014) Decreased expression of interleukin-36α predicts poor prognosis in colorectal cancer patients. Int J Clin Exp Pathol 7:8077–8081PubMedPubMedCentral
Metadaten
Titel
Association of IL-36γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer
verfasst von
Aliyah M. Weinstein
Nicolas A. Giraldo
Florent Petitprez
Catherine Julie
Laetitia Lacroix
Frédérique Peschaud
Jean-François Emile
Laetitia Marisa
Wolf H. Fridman
Walter J. Storkus
Catherine Sautès-Fridman
Publikationsdatum
12.10.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 1/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-018-2259-0

Weitere Artikel der Ausgabe 1/2019

Cancer Immunology, Immunotherapy 1/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.