Association of IL-36γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer - Centre de recherche des Cordeliers
Article Dans Une Revue Cancer Immunology, Immunotherapy Année : 2019

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

Résumé

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.
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Dates et versions

hal-04691107 , version 1 (07-09-2024)

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Aliyah M Weinstein, Nicolas A Giraldo, Florent Petitprez, Catherine Julie, Laetitia Lacroix, et al.. Association of IL-36γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer. Cancer Immunology, Immunotherapy, 2019, 68 (1), pp.109-120. ⟨10.1007/s00262-018-2259-0⟩. ⟨hal-04691107⟩
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