Skip to Main content Skip to Navigation
Journal articles

The Caspase-1/IL-18 Axis of the Inflammasome in Tumor Cells: A Modulator of the Th1/Tc1 Response of Tumor-Infiltrating T Lymphocytes in Colorectal Cancer

Abstract : In colorectal cancer (CRC), a high density of T lymphocytes represents a strong prognostic marker in subtypes of CRC. Optimized immunotherapy strategies to boost this T-cell response are still needed. A good candidate is the inflammasome pathway, an emerging player in cancer immunology that bridges innate and adaptive immunity. Its effector protein caspase-1 matures IL-18 that can promote a T-helper/cytotoxic (Th1/Tc1) response. It is still unknown whether tumor cells from CRC possess a functional caspase-1/IL-18 axis that could modulate the Th1/Tc1 response. We used two independent cohorts of CRC patients to assess IL-18 and caspase-1 expression by tumor cells in relation to the density of TILs and the microsatellite status of CRC. Functional and multiparametric approaches at the protein and mRNA levels were performed on an ex vivo CRC explant culture model. We show that, in the majority of CRCs, tumor cells display an activated and functional caspase-1/IL-18 axis that contributes to drive a Th1/Tc1 response elicited by TILs expressing IL-18Rα. Furthermore, unsupervised clustering identified three clusters of CRCs according to the caspase-1/IL-18/TIL density/interferon gamma (IFNγ) axis and microsatellite status. Together, our results strongly suggest that targeting the caspase-1/IL-18 axis can improve the anti-tumor immune response in subgroups of CRC.
Document type :
Journal articles
Complete list of metadata

https://www.hal.inserm.fr/inserm-03287920
Contributor : Elizabeth Bernardo <>
Submitted on : Friday, July 16, 2021 - 8:23:37 AM
Last modification on : Thursday, July 29, 2021 - 3:35:55 AM

File

Bilonda2021Eq3.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Linda Mutala, Cécile Deleine, Matilde Karakachoff, Delphine Dansette, Kathleen Ducoin, et al.. The Caspase-1/IL-18 Axis of the Inflammasome in Tumor Cells: A Modulator of the Th1/Tc1 Response of Tumor-Infiltrating T Lymphocytes in Colorectal Cancer. Cancers, MDPI, 2021, 13 (2), pp.189. ⟨10.3390/cancers13020189⟩. ⟨inserm-03287920⟩

Share

Metrics

Record views

32

Files downloads

57