{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:29:49Z","timestamp":1793039389923,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Blodcancerfonden","award":["2024"],"award-info":[{"award-number":["2024"]}]},{"name":"Blodcancerfonden","award":["200726"],"award-info":[{"award-number":["200726"]}]},{"name":"Blodcancerfonden","award":["221272"],"award-info":[{"award-number":["221272"]}]},{"name":"Blodcancerfonden","award":["10347"],"award-info":[{"award-number":["10347"]}]},{"name":"Blodcancerfonden","award":["10665"],"award-info":[{"award-number":["10665"]}]},{"name":"Blodcancerfonden","award":["10952"],"award-info":[{"award-number":["10952"]}]},{"name":"Blodcancerfonden","award":["FoUI-960534"],"award-info":[{"award-number":["FoUI-960534"]}]},{"name":"The Swedish Cancer Society","award":["2024"],"award-info":[{"award-number":["2024"]}]},{"name":"The Swedish Cancer Society","award":["200726"],"award-info":[{"award-number":["200726"]}]},{"name":"The Swedish Cancer Society","award":["221272"],"award-info":[{"award-number":["221272"]}]},{"name":"The Swedish Cancer Society","award":["10347"],"award-info":[{"award-number":["10347"]}]},{"name":"The Swedish Cancer Society","award":["10665"],"award-info":[{"award-number":["10665"]}]},{"name":"The Swedish Cancer Society","award":["10952"],"award-info":[{"award-number":["10952"]}]},{"name":"The Swedish Cancer Society","award":["FoUI-960534"],"award-info":[{"award-number":["FoUI-960534"]}]},{"name":"The Swedish Cancer and Allergy Foundation","award":["2024"],"award-info":[{"award-number":["2024"]}]},{"name":"The Swedish Cancer and Allergy Foundation","award":["200726"],"award-info":[{"award-number":["200726"]}]},{"name":"The Swedish Cancer and Allergy Foundation","award":["221272"],"award-info":[{"award-number":["221272"]}]},{"name":"The Swedish Cancer and Allergy Foundation","award":["10347"],"award-info":[{"award-number":["10347"]}]},{"name":"The Swedish Cancer and Allergy Foundation","award":["10665"],"award-info":[{"award-number":["10665"]}]},{"name":"The Swedish Cancer and Allergy Foundation","award":["10952"],"award-info":[{"award-number":["10952"]}]},{"name":"The Swedish Cancer and Allergy Foundation","award":["FoUI-960534"],"award-info":[{"award-number":["FoUI-960534"]}]},{"name":"Region Stockholm (A.L.F.)","award":["2024"],"award-info":[{"award-number":["2024"]}]},{"name":"Region Stockholm (A.L.F.)","award":["200726"],"award-info":[{"award-number":["200726"]}]},{"name":"Region Stockholm (A.L.F.)","award":["221272"],"award-info":[{"award-number":["221272"]}]},{"name":"Region Stockholm (A.L.F.)","award":["10347"],"award-info":[{"award-number":["10347"]}]},{"name":"Region Stockholm (A.L.F.)","award":["10665"],"award-info":[{"award-number":["10665"]}]},{"name":"Region Stockholm (A.L.F.)","award":["10952"],"award-info":[{"award-number":["10952"]}]},{"name":"Region Stockholm (A.L.F.)","award":["FoUI-960534"],"award-info":[{"award-number":["FoUI-960534"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Nurse-like cells (NLCs) derived from monocytes in the tumor microenvironment support the growth of chronic lymphocytic leukemia (CLL) cells. Here, we investigated the effects of a CX3CR1 (fractalkine receptor) antagonist (KAND567) on autologous monocytes and their pro-survival effects on CLL cells in vitro. Methods: Plasma concentration of CX3CL1 was determined by ELISA and CX3CR1 expression by flow cytometry. CD19+ cells and autologous monocytes from patients with CLL and healthy donors were treated with KAND567 either in co-culture or alone. The apoptosis of CD19+ cells and monocytes was determined by Annexin V\/PI staining and live-cell imaging. Results: Plasma concentration of CX3CL1 (fractalkine) was significantly higher in patients with CLL (n = 88) than in healthy donors (n = 32) (p &lt; 0.0001), with higher levels in patients with active compared to non-active disease (p &lt; 0.01). CX3CR1 was found on monocytes but not B cells in patients and controls. Levels of intermediate and non-classical CX3CR1+ monocytes were higher in patients with CLL than in controls (p &lt; 0.001), particularly in those with active disease (p &lt; 0.0001). Co-culture experiments revealed that autologous monocytes promoted the survival of both malignant and normal B cells and that KAND567 selectively inhibited the growth of CLL cells in a dose-dependent manner but only in the presence of autologous monocytes (p &lt; 0.05). Additionally, KAND567 inhibited the transition of monocytes to NLCs in CLL (p &lt; 0.05). Conclusions: Our data suggest that the CX3CR1\/CX3CL1 axis is activated in CLL and may contribute to the NLC-driven growth-promoting effects of CLL cells. KAND567, which is in clinical trials in other disorders, should also be explored in CLL.<\/jats:p>","DOI":"10.3390\/cancers16223821","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T09:59:11Z","timestamp":1731491951000},"page":"3821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Small Molecule Antagonist of CX3CR1 (KAND567) Inhibited the Tumor Growth-Promoting Effect of Monocytes in Chronic Lymphocytic Leukemia (CLL)"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5374-147X","authenticated-orcid":false,"given":"Wen","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6544-4209","authenticated-orcid":false,"given":"Parviz","family":"Kokhaei","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"},{"name":"Department of Immunology, Arak University of Medical Sciences, Arak 3848170001, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6554-3263","authenticated-orcid":false,"given":"Tom A.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"},{"name":"Department of Hematology, Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amineh","family":"Ghaderi","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Moshfegh","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Lundin","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"},{"name":"Department of Hematology, Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"},{"name":"Department of Hematology, Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Schultz","sequence":"additional","affiliation":[{"name":"Kancera AB, Karolinska Institutet Science Park, SE-17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Olin","sequence":"additional","affiliation":[{"name":"Kancera AB, Karolinska Institutet Science Park, SE-17165 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"\u00d6sterborg","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"},{"name":"Department of Hematology, Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Mellstedt","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0589-5523","authenticated-orcid":false,"given":"Mohammad","family":"Hojjat-Farsangi","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm and Karolinska Institute, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/ajh.25595","article-title":"Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment","volume":"94","author":"Hallek","year":"2019","journal-title":"Am. 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