{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:38:36Z","timestamp":1780634316482,"version":"3.54.1"},"reference-count":25,"publisher":"American Society of Hematology","issue":"23","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Autologous stem cell transplantation (ASCT) with maintenance lenalidomide remains the mainstay of consolidation therapy for eligible patients with multiple myeloma, but preventing disease relapse remains a critical unmet need. Here, we investigated whether immunosuppressive myeloid populations in bone marrow correlated with ASCT outcomes. We identified a subset of CD64+CD169+CD163+ macrophages that expressed CSF-1R, PD-L1, and CD155 and were expanded in patients who relapsed after ASCT. Using a preclinical ASCT model with suboptimal endogenous antimyeloma activity, we demonstrated that although neither CSF-1R inhibition nor lenalidomide monotherapy significantly improved outcomes, their combination synergistically attenuated disease progression and prolonged survival. Single-cell RNA sequencing revealed that lenalidomide expanded natural killer (NK)\u2013like CD8+ T cells but paradoxically also increased the frequency of Csf1r+ macrophages. Cell-cell communication analyses identified Csf1r+ macrophages as suppressors of these NK- and effector-like phenotypically exhausted (Tphex) CD8 T-cell populations through CD94\/NKG2A and PD-L1\/PD-1, respectively. CSF-1R blockade depleted these immunosuppressive macrophages, which correlated with decreased expression of inhibitory receptors and enhanced expression of activation markers in Tphex. Given the US Food and Drug Administration approval of axatilimab for chronic graft-versus-host disease, combining CSF-1R blockade with lenalidomide maintenance represents a readily testable strategy to improve progression-free survival after ASCT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025030207","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T18:36:58Z","timestamp":1772476618000},"page":"2786-2792","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell transplantation"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-9264","authenticated-orcid":false,"given":"Simone A.","family":"Minnie","sequence":"first","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"2Department of Medicine, University of California, San Francisco, San Francisco, CA"},{"name":"3Parker Institute for Cancer Immunotherapy, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1966-7163","authenticated-orcid":false,"given":"Kenneth","family":"Ho","sequence":"additional","affiliation":[{"name":"2Department of Medicine, University of California, San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1378-4752","authenticated-orcid":false,"given":"Julie R.","family":"Boiko","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"4Department of Pediatrics, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3248-587X","authenticated-orcid":false,"given":"Rachael C.","family":"Adams","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen S.","family":"Ensbey","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole S.","family":"Nemychenkov","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel R. W.","family":"Legg","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2051-0825","authenticated-orcid":false,"given":"Christine R.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"5Neural Dynamics Department, Allen Institute, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa L.","family":"Comstock","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina M.","family":"Lyons","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Sekiguchi","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoko","family":"Koyama","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Spencer","sequence":"additional","affiliation":[{"name":"6Australian Centre for Blood Diseases, Alfred Health-Monash University, Melbourne, VIC, Australia"},{"name":"7Department of Malignant Hematology and Stem Cell Transplantation, Alfred Health, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0477-1446","authenticated-orcid":false,"given":"Damian J.","family":"Green","sequence":"additional","affiliation":[{"name":"8Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey R.","family":"Hill","sequence":"additional","affiliation":[{"name":"1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"9Division of Medical Oncology, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"2","key":"2026060411214189900_bib1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1056\/NEJMoa2204925","article-title":"Triplet therapy, transplantation, and maintenance until progression in myeloma","volume":"387","author":"Richardson","year":"2022","journal-title":"N Engl J Med"},{"issue":"1","key":"2026060411214189900_bib2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1172\/JCI98888","article-title":"Bone marrow transplantation generates T-cell-dependent control of myeloma in mice","volume":"129","author":"Vuckovic","year":"2019","journal-title":"J Clin Invest"},{"issue":"16","key":"2026060411214189900_bib3","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1182\/blood-2018-01-825240","article-title":"Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade","volume":"132","author":"Minnie","year":"2018","journal-title":"Blood"},{"issue":"94","key":"2026060411214189900_bib4","doi-asserted-by":"crossref","first-page":"eadg1094","DOI":"10.1126\/sciimmunol.adg1094","article-title":"TIM-3+ CD8 T-cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies","volume":"9","author":"Minnie","year":"2024","journal-title":"Sci Immunol"},{"issue":"4","key":"2026060411214189900_bib5","doi-asserted-by":"crossref","DOI":"10.1172\/JCI157907","article-title":"TIGIT inhibition and lenalidomide synergistically promote antimyeloma immune responses after stem cell transplantation in mice","volume":"133","author":"Minnie","year":"2023","journal-title":"J Clin Invest"},{"issue":"10","key":"2026060411214189900_bib6","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1182\/blood.2024025680","article-title":"The contribution of the monocyte-macrophage lineage to immunotherapy outcomes","volume":"145","author":"Adams","year":"2025","journal-title":"Blood"},{"issue":"2","key":"2026060411214189900_bib7","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1182\/blood.2024025231","article-title":"Single-cell analysis of the multiple myeloma microenvironment after gamma-secretase inhibition and CAR T-cell therapy","volume":"145","author":"Coffey","year":"2025","journal-title":"Blood"},{"issue":"1","key":"2026060411214189900_bib8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40425-018-0491-y","article-title":"Different role of circulating myeloid-derived suppressor cells in patients with multiple myeloma undergoing autologous stem cell transplantation","volume":"7","author":"Lee","year":"2019","journal-title":"J Immunother Cancer"},{"issue":"1","key":"2026060411214189900_bib9","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/leu.2017.193","article-title":"Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma","volume":"32","author":"Wang","year":"2018","journal-title":"Leukemia"},{"issue":"6","key":"2026060411214189900_bib10","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.ccr.2014.05.016","article-title":"Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy","volume":"25","author":"Ries","year":"2014","journal-title":"Cancer cell"},{"issue":"4","key":"2026060411214189900_bib11","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.immuni.2013.04.004","article-title":"Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes","volume":"38","author":"Hashimoto","year":"2013","journal-title":"Immunity"},{"issue":"1","key":"2026060411214189900_bib12","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","article-title":"Macrophage diversity enhances tumor progression and metastasis","volume":"141","author":"Qian","year":"2010","journal-title":"Cell"},{"issue":"9","key":"2026060411214189900_bib13","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-004219","article-title":"Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer","volume":"10","author":"Zhu","year":"2022","journal-title":"J Immunother Cancer"},{"issue":"6","key":"2026060411214189900_bib14","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.146707","article-title":"Hedgehog-induced PD-L1 on tumor-associated macrophages is critical for suppression of tumor-infiltrating CD8+ T-cell function","volume":"6","author":"Petty","year":"2021","journal-title":"JCI insight"},{"issue":"14","key":"2026060411214189900_bib15","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1182\/blood-2018-05-852798","article-title":"Crbn (I391V) is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice","volume":"132","author":"Fink","year":"2018","journal-title":"Blood"},{"issue":"11","key":"2026060411214189900_bib16","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.7150\/thno.109097","article-title":"Spatially segregated APOE(+) macrophages restrict immunotherapy efficacy in clear cell renal cell carcinoma","volume":"15","author":"Ge","year":"2025","journal-title":"Theranostics"},{"issue":"16","key":"2026060411214189900_bib17","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1158\/0008-5472.CAN-20-3929","article-title":"Apolipoprotein E promotes immune suppression in pancreatic cancer through NF-\u03baB\u2013mediated production of CXCL1","volume":"81","author":"Kemp","year":"2021","journal-title":"Cancer Res"},{"issue":"2","key":"2026060411214189900_bib18","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cmet.2007.06.010","article-title":"PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties","volume":"6","author":"Bouhlel","year":"2007","journal-title":"Cell Metab"},{"issue":"13","key":"2026060411214189900_bib19","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1182\/bloodadvances.2023012416","article-title":"CD4+ CAR T-cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR T-cell therapy","volume":"8","author":"Ledergor","year":"2024","journal-title":"Blood Adv"},{"issue":"9","key":"2026060411214189900_bib20","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.ccell.2022.08.005","article-title":"NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer","volume":"40","author":"Salom\u00e9","year":"2022","journal-title":"Cancer cell"},{"issue":"26","key":"2026060411214189900_bib21","doi-asserted-by":"crossref","first-page":"E5980","DOI":"10.1073\/pnas.1720564115","article-title":"Distinct human circulating NKp30+Fc3RIy+CD8+ T-cell population exhibiting high natural killer-like antitumor potential","volume":"115","author":"Correia","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"2026060411214189900_bib22","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.ymthe.2021.10.011","article-title":"IL12 integrated into the CAR exodomain converts CD8+T-cells to poly-functional NK-like cells with superior killing of antigen-loss tumors","volume":"30","author":"Hombach","year":"2022","journal-title":"Mol Ther"},{"issue":"9","key":"2026060411214189900_bib23","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/s43018-023-00600-4","article-title":"CD8+ T-cells maintain killing of MHC-I-negative tumor cells through the NKG2D\u2013NKG2DL axis","volume":"4","author":"Lerner","year":"2023","journal-title":"Nat Cancer"},{"issue":"10","key":"2026060411214189900_bib24","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.1172\/JCI75935","article-title":"CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease","volume":"124","author":"Alexander","year":"2014","journal-title":"J Clin Invest"},{"issue":"11","key":"2026060411214189900_bib25","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1056\/NEJMoa2401537","article-title":"Axatilimab in recurrent or refractory chronic graft-versus-host disease","volume":"391","author":"Wolff","year":"2024","journal-title":"N Engl J Med"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/23\/2786\/2524494\/blood_bld-2025-030207-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/147\/23\/2786\/2524494\/blood_bld-2025-030207-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:21:50Z","timestamp":1780586510000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/147\/23\/2786\/566889\/CSF-1R-inhibition-and-lenalidomide-synergize-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":25,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2026,6,4]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2025030207","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6,4]]},"published":{"date-parts":[[2026,6,4]]}}}