en
Scientific article
Open access
English

IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia

Published inHaematologica
Publication date2023-04-06
First online date2023-04-06
Abstract

Chronic Myeloid Leukemia (CML) is a hematologic malignancy associated to an unregulated growth of myeloid cells in Bone Marrow (BM) and Peripheral Blood (PB), characterized by the BCR-ABL1 translocation. Given the known cytokine impairment in the leukemic niche of CML, we investigated the impact of this microenvironmental dysregulation on Innate Lymphoid Cells (ILCs), whose role in cancer has recently emerged. Three ILC subsets are identified based on transcriptional profiles and cytokine secretion. We observed that IL-18 and VEGF-A are increased in CML patients’ sera and that ILC2s are enriched in CML PB and BM. We found that IL-18 drives ILC2 proliferation and that CML ILC2s highly express CXCR4 and CXCR7 BM-homing receptors, potentially explaining their enrichment in PB and BM, respectively. Next, we showed that ILC2s are hyper-activated through a tumor-derived VEGF-A-dependent mechanism, which leads to higher IL-13 secretion. In response to IL-13, leukemic cells increase their clonogenic capacity. Finally, we discovered that the pro-tumoral axis involving VEGF-A, IL-18 and ILC2s was disrupted upon Tyrosine Kinase Inhibitors’ (TKIs) treatment, normalizing the levels of all these players in CML patients responding to therapy. Overall, our study uncovers the involvement of ILC2s in CML progression, mediated by VEGF-A and IL-18.

eng
Citation (ISO format)
FIORDI, Benedetta et al. IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia. In: Haematologica, 2023. doi: 10.3324/haematol.2022.282140
Main files (1)
Article (Published version)
Secondary files (1)
Identifiers
ISSN of the journal0390-6078
23views
8downloads

Technical informations

Creation08/13/2023 1:13:26 PM
First validation08/14/2023 7:31:12 AM
Update time08/14/2023 7:31:12 AM
Status update08/14/2023 7:31:12 AM
Last indexation02/12/2024 1:48:06 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack