{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:56:34Z","timestamp":1786982194795,"version":"build-2736575974"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100018694","name":"HORIZON EUROPE Marie Sklodowska-Curie Actions","doi-asserted-by":"crossref","award":["813871"],"award-info":[{"award-number":["813871"]}],"id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018694","name":"HORIZON EUROPE Marie Sklodowska-Curie Actions","doi-asserted-by":"crossref","award":["813871"],"award-info":[{"award-number":["813871"]}],"id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Immunol Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute myeloid leukaemia is an aggressive hematologic malignancy that remains exceedingly difficult to treat despite recent advancements. High expression of CD47 on leukemic blasts interacts with the inhibitory receptor SIRP-alpha (SIRP-\u03b1) on innate immune cells, resulting in a strong \"don't eat me\" signal. Therefore, identifying AML patients who could benefit from immune-targeted therapies is crucial SIRP-\u03b22 is predominantly expressed in myeloid cells and positively regulates innate anticancer immunity. Furthermore, endogenously expressed SIRP-\u03b22 potentiates cancer cell trogocytosis by granulocytes. Here, we delineate the role of SIRP-\u03b22 in AML. High expression of SIRP-\u03b22 is independently associated with favorable overall survival (OS) and event free survival (EFS) independent of the ELN intermediate risk group. SIRP-\u03b22 is more prevalent in the more committed FAB M4 and M5 subgroups. SIRP-\u03b22 is also expressed on normal myeloid cells in patient samples, with higher expression on tumor-suppressive M1 macrophages than on adverse prognostic and tumor-supportive M2 macrophages. In line with this, co-culture of macrophages\/neutrophils with ectopically expressed SIRP-\u03b22 tumor cells results in an increased phagocytosis\/trogocytosis treated with anti-CD47. These data indicate that AML patients with high SIRP-\u03b22 AML expression could significantly benefit from innate immune-targeting therapies such as CD47 immune checkpoint inhibitor.<\/jats:p>","DOI":"10.1007\/s12026-025-09659-w","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T06:01:17Z","timestamp":1750831277000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High expression of signal regulatory protein beta 2 marks a favourable prognostic AML subgroup and associates with increased sensitivity to phagocytosis"],"prefix":"10.1007","volume":"73","author":[{"given":"Nienke","family":"Visser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha K.","family":"van der Meer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerwin","family":"Huls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Jacob","family":"Schuringa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Bremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"issue":"1","key":"9659_CR1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","volume":"12","author":"D Hanahan","year":"2022","unstructured":"Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31\u201346. https:\/\/doi.org\/10.1158\/2159-8290.CD-21-1059.","journal-title":"Cancer Discov"},{"key":"9659_CR2","doi-asserted-by":"publisher","unstructured":"Daver, N. G., Vyas, P., Kambhampati, S., Al Malki, M. M., Larson, R. A., Asch, A. S., Mannis, G., Chai-Ho, W., Tanaka, T. N., Bradley, T. J., Jeyakumar, D., Wang, E. S., Sweet, K., Kantarjian, H. M., Garcia-Manero, G., Komrokji, R., Xing, G., Ramsingh, G., Renard, C., \u2026 Sallman, D. A. (2023). Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined With Azacitidine in Patients With Previously Untreated AML: Phase Ib Results. Journal of Clinical Oncology\u202f: Official Journal of the American Society of Clinical Oncology, 41(31), 4893\u20134904. https:\/\/doi.org\/10.1200\/JCO.22.02604","DOI":"10.1200\/JCO.22.02604"},{"key":"9659_CR3","unstructured":"NCT04778397. (2023). Study of Magrolimab in Combination With Azacitidine Versus Physician\u2019s Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Patients With TP53 Mutant Acute Myeloid Leukemia That Have Not Been Treated (ENHANCE-2). ClinicalTrial."},{"issue":"5","key":"9659_CR4","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.cell.2010.07.044","volume":"142","author":"MP Chao","year":"2010","unstructured":"Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, Jan M, Cha AC, Chan CK, Tan BT, Park CY, Zhao F, Kohrt HE, Malumbres R, Briones J, Gascoyne RD, Lossos IS, Levy R, Weissman IL, Majeti R. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell. 2010;142(5):699\u2013713. https:\/\/doi.org\/10.1016\/j.cell.2010.07.044.","journal-title":"Cell"},{"issue":"2","key":"9659_CR5","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1386361","volume":"7","author":"PE van Bommel","year":"2018","unstructured":"van Bommel PE, He Y, Schepel I, Hendriks MAJM, Wiersma VR, van Ginkel RJ, van Meerten T, Ammatuna E, Huls G, Samplonius DF, Helfrich W, Bremer E. CD20-selective inhibition of CD47-SIRP\u03b1 \u201cdon\u2019t eat me\u201d signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab. Oncoimmunology. 2018;7(2). https:\/\/doi.org\/10.1080\/2162402X.2017.1386361.","journal-title":"Oncoimmunology"},{"key":"9659_CR6","doi-asserted-by":"publisher","first-page":"1287256","DOI":"10.3389\/fimmu.2023.1287256","volume":"14","author":"N Visser","year":"2023","unstructured":"Visser N, Nelemans LC, He Y, Lourens HJ, Corrales MG, Huls G, Wiersma VR, Schuringa JJ, Bremer E. Signal regulatory protein beta 2 is a novel positive regulator of innate anticancer immunity. Front Immunol. 2023;14:1287256. https:\/\/doi.org\/10.3389\/fimmu.2023.1287256.","journal-title":"Front Immunol"},{"issue":"D1","key":"9659_CR7","doi-asserted-by":"publisher","first-page":"D881","DOI":"10.1093\/nar\/gky1076","volume":"47","author":"FO Bagger","year":"2019","unstructured":"Bagger FO, Kinalis S, Rapin N. BloodSpot: a database of healthy and malignant haematopoiesis updated with purified and single cell mRNA sequencing profiles. Nucleic Acids Res. 2019;47(D1):D881\u20135. https:\/\/doi.org\/10.1093\/nar\/gky1076.","journal-title":"Nucleic Acids Res"},{"key":"9659_CR8","doi-asserted-by":"publisher","unstructured":"van Beek, E. M., Cochrane, F., Barclay, A. N., & van den Berg, T. K. (2005). Signal regulatory proteins in the immune system. Journal of Immunology (Baltimore, Md.\u202f: 1950), 175(12), 7781\u20137787. https:\/\/doi.org\/10.4049\/jimmunol.175.12.7781","DOI":"10.4049\/jimmunol.175.12.7781"},{"issue":"2","key":"9659_CR9","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.cell.2009.05.045","volume":"138","author":"R Majeti","year":"2009","unstructured":"Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD, van Rooijen N, Weissman IL. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138(2):286\u201399. https:\/\/doi.org\/10.1016\/j.cell.2009.05.045.","journal-title":"Cell"},{"issue":"5","key":"9659_CR10","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1182\/blood-2003-06-1978","volume":"103","author":"R Zheng","year":"2004","unstructured":"Zheng R, Friedman AD, Levis M, Li L, Weir EG, Small D. Internal tandem duplication mutation of FLT3 blocks myeloid differentiation through suppression of C\/EBPalpha expression. Blood. 2004;103(5):1883\u201390. https:\/\/doi.org\/10.1182\/blood-2003-06-1978.","journal-title":"Blood"},{"issue":"Supplement 1","key":"9659_CR11","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1182\/blood-2023-187695","volume":"142","author":"J Sango","year":"2023","unstructured":"Sango J, Carcamo S, Cruz-Rodriguez N, Sirenko M, Maiti A, Olszewska M, Wang T, Ulukaya GB, Tomalin L, Olivier E, Jaud M, Chaligne R, Mansour H, Demircioglu D, Landau DA, Papaemmanuil E, DiNardo CD, Hasson D, Konopleva MY, Papapetrou E. N\/KRAS -Mutant AML LSCs Originate from Committed Myelomonocytic Progenitors and Drive Clinical Resistance to Venetoclax. Blood. 2023;142(Supplement 1):403\u2013403. https:\/\/doi.org\/10.1182\/blood-2023-187695.","journal-title":"Blood"},{"issue":"8","key":"9659_CR12","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1002\/ijc.29945","volume":"138","author":"L Andzinski","year":"2016","unstructured":"Andzinski L, Kasnitz N, Stahnke S, Wu C-F, Gereke M, von K\u00f6ckritz-Blickwede M, Schilling B, Brandau S, Weiss S, Jablonska J. Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human. Int J Cancer. 2016;138(8):1982\u201393. https:\/\/doi.org\/10.1002\/ijc.29945.","journal-title":"Int J Cancer"},{"key":"9659_CR13","doi-asserted-by":"publisher","DOI":"10.3791\/52933","volume":"100","author":"RV Sionov","year":"2015","unstructured":"Sionov RV, Assi S, Gershkovitz M, Sagiv JY, Polyansky L, Mishalian I, Fridlender ZG, Granot Z. Isolation and Characterization of Neutrophils with Anti-Tumor Properties. Journal of Visualized Experiments\u202f: JoVE. 2015;100. https:\/\/doi.org\/10.3791\/52933.","journal-title":"Journal of Visualized Experiments : JoVE"}],"container-title":["Immunologic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-025-09659-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12026-025-09659-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-025-09659-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T07:30:20Z","timestamp":1770190220000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12026-025-09659-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,25]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["9659"],"URL":"https:\/\/doi.org\/10.1007\/s12026-025-09659-w","relation":{},"ISSN":["0257-277X","1559-0755"],"issn-type":[{"value":"0257-277X","type":"print"},{"value":"1559-0755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,25]]},"assertion":[{"value":"10 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Peripheral blood (PB) and bone marrow (BM) samples of AML patients were studied after informed consent and protocol approval by the Medical Ethical committee of the UMCG in accordance with the Declaration of Helsinki (protocol code NL43844.042.13, 6 January 2014).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"98"}}