{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:30:30Z","timestamp":1794047430783,"version":"4.8.0"},"reference-count":50,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"9","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>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 (ILC), whose role in cancer has recently emerged. Three ILC subsets are identified based on transcriptional profiles and cytokine secretion. We observed that interleukin 18 (IL-18) and vascular endothelial growth factor A (VEGF-A) are increased in CML patients\u2019 sera and that ILC2 are enriched in CML PB and BM. We found that IL-18 drives ILC2 proliferation and that CML ILC2 highly express CXCR4 and CXCR7 BM-homing receptors, potentially explaining their enrichment in PB and BM, respectively. Next, we showed that ILC2 are hyper-activated through a tumor-derived VEGF-Adependent 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 ILC2 was disrupted upon tyrosine kinase inhibitor treatment, normalizing the levels of all these players in CML patients responding to therapy. Overall, our study uncovers the involvement of ILC2 in CML progression, mediated by VEGF-A and IL-18.<\/jats:p>","DOI":"10.3324\/haematol.2022.282140","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T04:05:48Z","timestamp":1680753948000},"page":"2396-2409","source":"Crossref","is-referenced-by-count":11,"title":["IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia"],"prefix":"10.3324","volume":"108","author":[{"given":"Benedetta","family":"Fiordi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Salvestrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Gugliotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Castagnetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Curti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Speiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Marcenaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Jandus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Trabanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"51426","doi-asserted-by":"crossref","unstructured":"Cortes J, Pavlovsky C, Sau\u00dfele S. Chronic myeloid leukaemia. Lancet. 2021; 398(10314):1914-1926.","DOI":"10.1016\/S0140-6736(21)01204-6"},{"key":"51427","doi-asserted-by":"crossref","unstructured":"Deininger MWN, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood. 2000; 96(10):3343-3356.","DOI":"10.1182\/blood.V96.10.3343.h8003343_3343_3356"},{"key":"51428","doi-asserted-by":"crossref","unstructured":"Osman AEG, Deininger MW. Chronic myeloid leukemia: modern therapies, current challenges and future directions. Blood Rev. 2021; 49:100825.","DOI":"10.1016\/j.blre.2021.100825"},{"key":"51429","doi-asserted-by":"crossref","unstructured":"Spits H, di Santo JP. The expanding family of innate lymphoid cells: Regulators and effectors of immunity and tissue remodeling. Nat Immunol. 2011; 12(1):21-27.","DOI":"10.1038\/ni.1962"},{"key":"51430","doi-asserted-by":"crossref","unstructured":"Ercolano G, Wyss T, Salom\u00e9 B, Romero P, Trabanelli S, Jandus C. Distinct and shared gene expression for human innate versus adaptive helper lymphoid cells. J Leukoc Biol. 2020; 108(2):723-737.","DOI":"10.1002\/JLB.5MA0120-209R"},{"key":"51431","doi-asserted-by":"crossref","unstructured":"Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015; 517(7534):293-301.","DOI":"10.1038\/nature14189"},{"key":"51432","doi-asserted-by":"crossref","unstructured":"Lim AI, Li Y, Lopez-Lastra S. Systemic human ILC precursors provide a substrate for tissue ILC differentiation. Cell. 2017; 168(6):1086-1100.","DOI":"10.1016\/j.cell.2017.02.021"},{"key":"51433","doi-asserted-by":"crossref","unstructured":"Ercolano G, Moretti A, Falquet M. Gliadin-reactive vitamin D-sensitive proinflammatory ILCPs are enriched in celiac patients. Cell Rep. 2022; 39(11):110956.","DOI":"10.1016\/j.celrep.2022.110956"},{"key":"51434","doi-asserted-by":"crossref","unstructured":"Chung DC, Jacquelot N, Ghaedi M, Warner K, Ohashi PS. 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