PMID- 37021528
OWN - NLM
STAT- MEDLINE
DCOM- 20230908
LR  - 20230913
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 108
IP  - 9
DP  - 2023 Sep 1
TI  - IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral 
      function in chronic myeloid leukemia.
PG  - 2396-2409
LID - 10.3324/haematol.2022.282140 [doi]
AB  - 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' 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.
FAU - Fiordi, Benedetta
AU  - Fiordi B
AD  - Department of Pathology and Immunology, Faculty of Medicine, University of 
      Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne 
      Branch, Lausanne, Switzerland.
FAU - Salvestrini, Valentina
AU  - Salvestrini V
AD  - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Institute of Hematology << 
      Seragnoli >>, Bologna, Italy.
FAU - Gugliotta, Gabriele
AU  - Gugliotta G
AD  - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Institute of Hematology << 
      Seragnoli >>, Bologna, Italy.
FAU - Castagnetti, Fausto
AU  - Castagnetti F
AD  - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Institute of Hematology << 
      Seragnoli >>, Bologna, Italy.
FAU - Curti, Antonio
AU  - Curti A
AD  - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Institute of Hematology << 
      Seragnoli >>, Bologna, Italy.
FAU - Speiser, Daniel E
AU  - Speiser DE
AD  - Department of Oncology, Lausanne University Hospital (CHUV) and University of 
      Lausanne, Epalinges, Switzerland.
FAU - Marcenaro, Emanuela
AU  - Marcenaro E
AD  - Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy; 
      IRCCS Ospedale Policlinico San Martino, Genova, Italy.
FAU - Jandus, Camilla
AU  - Jandus C
AD  - Department of Pathology and Immunology, Faculty of Medicine, University of 
      Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne 
      Branch, Lausanne, Switzerland.
FAU - Trabanelli, Sara
AU  - Trabanelli S
AD  - Department of Pathology and Immunology, Faculty of Medicine, University of 
      Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne 
      Branch, Lausanne, Switzerland. sara.trabanelli@unige.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230901
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Interleukin-18)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - 0 (Interleukin-13)
SB  - IM
MH  - Humans
MH  - *Vascular Endothelial Growth Factor A
MH  - Immunity, Innate
MH  - Interleukin-18
MH  - Fusion Proteins, bcr-abl/metabolism
MH  - Interleukin-13
MH  - Lymphocytes/metabolism
MH  - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
PMC - PMC10483352
EDAT- 2023/04/07 06:00
MHDA- 2023/09/08 06:42
PMCR- 2023/04/06
CRDT- 2023/04/06 04:52
PHST- 2022/09/20 00:00 [received]
PHST- 2023/09/08 06:42 [medline]
PHST- 2023/04/07 06:00 [pubmed]
PHST- 2023/04/06 04:52 [entrez]
PHST- 2023/04/06 00:00 [pmc-release]
AID - 10.3324/haematol.2022.282140 [doi]
PST - epublish
SO  - Haematologica. 2023 Sep 1;108(9):2396-2409. doi: 10.3324/haematol.2022.282140.