{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T22:00:06Z","timestamp":1792533606779,"version":"4.5.0"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100013318","name":"Shanxi Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["201801D121223"],"award-info":[{"award-number":["201801D121223"]}],"id":[{"id":"10.13039\/501100013318","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013318","name":"Shanxi Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["201801D121223"],"award-info":[{"award-number":["201801D121223"]}],"id":[{"id":"10.13039\/501100013318","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003398","name":"Shanxi Scholarship Council of China","doi-asserted-by":"publisher","award":["2023-187"],"award-info":[{"award-number":["2023-187"]}],"id":[{"id":"10.13039\/501100003398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003398","name":"Shanxi Scholarship Council of China","doi-asserted-by":"publisher","award":["2023-187"],"award-info":[{"award-number":["2023-187"]}],"id":[{"id":"10.13039\/501100003398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013438","name":"Department of Human Resources and Social Security of Shanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013438","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although substantial quantities of potent therapies for multiple myeloma (MM) have been established, MM remains an incurable disease. In recent years, our understanding of the initiation, development, and metastasis of cancers has made a qualitative leap. Cancers attain the abilities to maintain proliferation signals, escape growth inhibitors, resist cell death, induce angiogenesis, and more importantly, escape anti-tumor immunity and reprogram metabolism, which are the hallmarks of cancers. Besides, different cancers have different tumor microenvironments (TME), thus, we pay more attention to the TME in the pathogenesis of MM. Many researchers have identified that myeloma cells interact with the components of TME, which is beneficial for their survival, ultimately causing the formation of immunosuppressive and high-metabolism TME. In the process, transforming growth factor-\u03b2 (TGF-\u03b2), as a pivotal cytokine in the TME, controls various cells\u2019 fates and influences numerous metabolic pathways, including inhibiting immune cells to infiltrate the tumors, suppressing the activation of anti-tumor immune cells, facilitating more immunosuppressive cells, enhancing glucose and glutamine metabolism, dysregulating bone metabolism and so on. Thus, we consider TGF-\u03b2 as the tumor promoter. However, in healthy cells and the early stage of tumors, it functions as a tumor suppressor. Due to the effect of context dependence, TGF-\u03b2 has dual roles in TME, which attracts us to further explore whether targeting it can overcome obstacles in the treatment of MM by regulating the progression of myeloma, molecular mechanisms of drug resistance, and various signaling pathways in the immune and metabolic microenvironment. In this review, we predominantly discuss that TGF-\u03b2 promotes the development of MM by influencing immunity and metabolism.<\/jats:p>","DOI":"10.1007\/s00277-024-05843-4","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T10:06:18Z","timestamp":1718877978000},"page":"4351-4362","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["TGF-\u03b2: an active participant in the immune and metabolic microenvironment of multiple myeloma"],"prefix":"10.1007","volume":"103","author":[{"given":"Han-Yue","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"5843_CR1","doi-asserted-by":"publisher","unstructured":"Brigle K (2017) Pathobiology and diagnosis of multiple myeloma [J]. Semin Oncol Nurs 33(3):225\u201336. https:\/\/doi.org\/10.1016\/j.soncn.2017.05.012","DOI":"10.1016\/j.soncn.2017.05.012"},{"key":"5843_CR2","unstructured":"Lucia Di Marzo1, VD*, Antonio Giovanni Solimando1 Ruggieri2, Tiziana Annese2, Beatrice Nico2, Ruggiero Fumarulo3, Simona, Angelo Vacca1, Frassanito3 AMA. (2016) Microenvironment drug resistance in multiple myeloma: emerging new players [J]. Oncotarget"},{"key":"5843_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1059715","author":"PS RANA","year":"2022","unstructured":"Rana PS, Soler DC, Kort J et al (2022) Targeting TGF-\u03b2 signaling in the multiple myeloma microenvironment: steering CARs and T cells in the right direction [J]. Front Cell Dev Biology. https:\/\/doi.org\/10.3389\/fcell.2022.1059715","journal-title":"Front Cell Dev Biology"},{"key":"5843_CR4","doi-asserted-by":"publisher","unstructured":"Harada T, Hiasa M, Teramachi J et al (2021) Myeloma\u2013Bone Interaction: a vicious cycle via TAK1\u2013PIM2 signaling [J]. Cancers 13(17). https:\/\/doi.org\/10.3390\/cancers13174441","DOI":"10.3390\/cancers13174441"},{"issue":"1","key":"5843_CR5","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1080\/15384101.2022.2109105","volume":"22","author":"J XIA","year":"2022","unstructured":"Xia J, Zhang Q, Luan J et al (2022) TGF\u03b2 signaling activation correlates with immune-inflamed tumor microenvironment across human cancers and predicts response to immunotherapy [J]. Cell Cycle 22(1):57\u201372. https:\/\/doi.org\/10.1080\/15384101.2022.2109105","journal-title":"Cell Cycle"},{"key":"5843_CR6","doi-asserted-by":"crossref","unstructured":"Takashi Maruyama AWC, A and Hiroyuki Shibata*,B. (2022) TGF-\u03b2 and cancer immunotherapy [J]. Biol Pharm Bull","DOI":"10.1248\/bpb.b21-00966"},{"key":"5843_CR7","doi-asserted-by":"publisher","unstructured":"Uckun FM (2021) Overcoming the immunosuppressive Tumor Microenvironment in multiple myeloma [J]. Cancers 13(9). https:\/\/doi.org\/10.3390\/cancers13092018","DOI":"10.3390\/cancers13092018"},{"issue":"3","key":"5843_CR8","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.soncn.2017.05.012","volume":"33","author":"K BRIGLE","year":"2017","unstructured":"Brigle K (2017) Pathobiology and diagnosis of multiple myeloma [J]. Semin Oncol Nurs 33(3):225\u20136. https:\/\/doi.org\/10.1016\/j.soncn.2017.05.012","journal-title":"Semin Oncol Nurs"},{"key":"5843_CR9","doi-asserted-by":"publisher","unstructured":"Zhong L, Hao P, Zhang Q et al (2022) Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM) [J]. Elife, 11. https:\/\/doi.org\/10.7554\/eLife.75340","DOI":"10.7554\/eLife.75340"},{"issue":"6","key":"5843_CR10","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1182\/blood-2005-11-013458","volume":"108","author":"F ZHAN","year":"2006","unstructured":"Zhan F, Huang Y, Colla S et al (2006) The molecular classification of multiple myeloma [J]. Blood 108(6):2020\u20132028. https:\/\/doi.org\/10.1182\/blood-2005-11-013458","journal-title":"Blood"},{"issue":"10","key":"5843_CR11","doi-asserted-by":"publisher","first-page":"3456","DOI":"10.1172\/JCI61188","volume":"122","author":"PL KUEHL W M, BERGSAGEL","year":"2012","unstructured":"Kuehl WM, Bergsagel PL (2012) Molecular pathogenesis of multiple myeloma and its premalignant precursor [J]. J Clin Invest 122(10):3456\u20133463. https:\/\/doi.org\/10.1172\/JCI61188","journal-title":"J Clin Invest"},{"issue":"3","key":"5843_CR12","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s12185-013-1291-2","volume":"97","author":"M CHESI","year":"2013","unstructured":"Chesi M, Bergsagel PL (2013) Molecular pathogenesis of multiple myeloma: basic and clinical updates [J]. Int J Hematol 97(3):313\u2013323. https:\/\/doi.org\/10.1007\/s12185-013-1291-2","journal-title":"Int J Hematol"},{"key":"5843_CR13","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13148-017-0319-5","volume":"9","author":"S ISSA M E, TAKHSHA F S, CHIRUMAMILLA","year":"2017","unstructured":"Issa ME, Takhsha FS, Chirumamilla CS et al (2017) Epigenetic strategies to reverse drug resistance in heterogeneous multiple myeloma [J]. Clin Epigenetics 9:17. https:\/\/doi.org\/10.1186\/s13148-017-0319-5","journal-title":"Clin Epigenetics"},{"key":"5843_CR14","doi-asserted-by":"publisher","first-page":"948548","DOI":"10.3389\/fonc.2022.948548","volume":"12","author":"J WANG","year":"2022","unstructured":"Wang J, Hu Y, Hamidi H et al (2022) Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling [J]. Front Oncol 12:948548. https:\/\/doi.org\/10.3389\/fonc.2022.948548","journal-title":"Front Oncol"},{"key":"5843_CR15","doi-asserted-by":"crossref","unstructured":"Jahangir Abdi1 GC, Hong Chang3,4,5 (2013) Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms [J]. Oncotarget","DOI":"10.18632\/oncotarget.1497"},{"issue":"37","key":"5843_CR16","doi-asserted-by":"publisher","first-page":"60698","DOI":"10.18632\/oncotarget.10849","volume":"7","author":"DESANTISV DI MARZO L","year":"2016","unstructured":"Di Marzo L, Desantis V, Solimando AG et al (2016) Microenvironment drug resistance in multiple myeloma: emerging new players [J]. Oncotarget 7(37):60698\u201360711. https:\/\/doi.org\/10.18632\/oncotarget.10849","journal-title":"Oncotarget"},{"key":"5843_CR17","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.ctrv.2018.09.001","volume":"70","author":"P ROBAK","year":"2018","unstructured":"Robak P, Drozdz I, Szemraj J et al (2018) Drug resistance in multiple myeloma [J]. Cancer Treat Rev 70:199\u2013208. https:\/\/doi.org\/10.1016\/j.ctrv.2018.09.001","journal-title":"Cancer Treat Rev"},{"key":"5843_CR18","doi-asserted-by":"publisher","unstructured":"Motais B, Charvatova S, Walek Z (2021) Selection, expansion, and unique pretreatment of allogeneic human natural killer cells with anti-CD38 monoclonal antibody for efficient multiple myeloma treatment [J]. Cells 10(5). https:\/\/doi.org\/10.3390\/cells10050967","DOI":"10.3390\/cells10050967"},{"key":"5843_CR19","doi-asserted-by":"publisher","unstructured":"Uckun FM (2021) Overcoming the immunosuppressive tumor microenvironment in multiple myeloma [J]. Cancers (Basel) 13(9). https:\/\/doi.org\/10.3390\/cancers13092018","DOI":"10.3390\/cancers13092018"},{"issue":"25","key":"5843_CR20","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1182\/blood-2016-01-691162","volume":"127","author":"ACHARYAC TAI Y-T","year":"2016","unstructured":"Tai Y-T, Acharya C, An G et al (2016) APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment [J]. Blood 127(25):3225\u20133236. https:\/\/doi.org\/10.1182\/blood-2016-01-691162","journal-title":"Blood"},{"key":"5843_CR21","doi-asserted-by":"publisher","first-page":"762","DOI":"10.3389\/fimmu.2020.00762","volume":"11","author":"M LEJEUNE","year":"2020","unstructured":"Lejeune M, Kose MC, Duray E et al (2020) Bispecific, T-Cell-recruiting antibodies in B-Cell malignancies [J]. Front Immunol 11:762. https:\/\/doi.org\/10.3389\/fimmu.2020.00762","journal-title":"Front Immunol"},{"issue":"5","key":"5843_CR22","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1111\/bjh.13889","volume":"172","author":"D ATANACKOVIC","year":"2016","unstructured":"Atanackovic D, Radhakrishnan SV, Bhardwaj N et al (2016) Chimeric Antigen Receptor (CAR) therapy for multiple myeloma [J]. Br J Haematol 172(5):685\u2013698. https:\/\/doi.org\/10.1111\/bjh.13889","journal-title":"Br J Haematol"},{"key":"5843_CR23","doi-asserted-by":"publisher","unstructured":"El Arfani C, De Veirman K, Maes K et al (2018) Metabolic features of multiple myeloma [J]. Int J Mol Sci 19(4). https:\/\/doi.org\/10.3390\/ijms19041200","DOI":"10.3390\/ijms19041200"},{"issue":"12","key":"5843_CR24","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/s41577-021-00541-y","volume":"21","author":"K DEPEAUX","year":"2021","unstructured":"Depeaux K, Delgoffe GM (2021) Metabolic barriers to cancer immunotherapy [J]. Nat Rev Immunol 21(12):785\u2013797. https:\/\/doi.org\/10.1038\/s41577-021-00541-y","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"5843_CR25","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1158\/0008-5472.CAN-11-2067","volume":"72","author":"JA FOWLER","year":"2012","unstructured":"Fowler JA, Mundy GR, Lwin ST et al (2012) Bone marrow stromal cells create a permissive microenvironment for myeloma development: a new stromal role for wnt inhibitor Dkk1 [J]. Cancer Res 72(9):2183\u20132189. https:\/\/doi.org\/10.1158\/0008-5472.CAN-11-2067","journal-title":"Cancer Res"},{"issue":"12","key":"5843_CR26","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1182\/blood-2016-03-707547","volume":"128","author":"G AN","year":"2016","unstructured":"An G, Acharya C, Feng X et al (2016) Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication [J]. Blood 128(12):1590\u20131603. https:\/\/doi.org\/10.1182\/blood-2016-03-707547","journal-title":"Blood"},{"issue":"22","key":"5843_CR27","doi-asserted-by":"publisher","first-page":"4766","DOI":"10.1158\/0008-5472.CAN-15-1320","volume":"75","author":"A PONZETTA","year":"2015","unstructured":"Ponzetta A, Benigni G, Antonangeli F et al (2015) Multiple myeloma impairs bone marrow localization of effector natural killer cells by altering the chemokine microenvironment [J]. Cancer Res 75(22):4766\u20134777. https:\/\/doi.org\/10.1158\/0008-5472.CAN-15-1320","journal-title":"Cancer Res"},{"issue":"5","key":"5843_CR28","doi-asserted-by":"publisher","first-page":"e561","DOI":"10.1097\/HS9.0000000000000561","volume":"5","author":"HOLTHOFLC STIKVOORT A","year":"2021","unstructured":"Holthof LC, Stikvoort A, Van Der Horst HJ et al (2021) Bone marrow mesenchymal stromal cell-mediated resistance in multiple myeloma against NK cells can be overcome by introduction of CD38-CAR or TRAIL-variant [J]. Hemasphere 5(5):e561. https:\/\/doi.org\/10.1097\/HS9.0000000000000561","journal-title":"Hemasphere"},{"issue":"17","key":"5843_CR29","doi-asserted-by":"publisher","first-page":"3625","DOI":"10.1182\/blood-2009-05-220285","volume":"114","author":"Y ZHENG","year":"2009","unstructured":"Zheng Y, Cai Z, Wang S et al (2009) Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis [J]. Blood 114(17):3625\u20133628. https:\/\/doi.org\/10.1182\/blood-2009-05-220285","journal-title":"Blood"},{"issue":"15","key":"5843_CR30","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1182\/blood-2012-08-448548","volume":"121","author":"G GORGUN G T, WHITEHILL","year":"2013","unstructured":"Gorgun GT, Whitehill G, Anderson JL et al (2013) Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans [J]. Blood 121(15):2975\u20132987. https:\/\/doi.org\/10.1182\/blood-2012-08-448548","journal-title":"Blood"},{"issue":"3","key":"5843_CR31","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.3390\/cancers6031363","volume":"6","author":"K DE VEIRMAN","year":"2014","unstructured":"De Veirman K, Rao L, De Bruyne E et al (2014) Cancer associated fibroblasts and tumor growth: focus on multiple myeloma [J]. Cancers (Basel) 6(3):1363\u20131381. https:\/\/doi.org\/10.3390\/cancers6031363","journal-title":"Cancers (Basel)"},{"key":"5843_CR32","doi-asserted-by":"publisher","unstructured":"M Urashima 1 AO, D Chauhan, M Hatziyanni, MB Vidriales, DA Dedera, RL Schlossman, KC Anderson (1996) Transforming growth factor-P 1: differential effects on multiple myeloma versus normal B cells [J]. The American Society of Hematology. https:\/\/doi.org\/10.1016\/S0006-4971(20)65303-4","DOI":"10.1016\/S0006-4971(20)65303-4"},{"key":"5843_CR33","doi-asserted-by":"publisher","first-page":"788","DOI":"10.3389\/fendo.2018.00788","volume":"9","author":"D HARMER","year":"2018","unstructured":"Harmer D, Falank C (2018) Interleukin-6 interweaves the bone marrow microenvironment, bone loss, and multiple myeloma [J]. Front Endocrinol (Lausanne) 9:788. https:\/\/doi.org\/10.3389\/fendo.2018.00788","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"5843_CR34","doi-asserted-by":"publisher","first-page":"4977","DOI":"10.1038\/s41467-020-18701-4","volume":"11","author":"M WERNER-KLEIN","year":"2020","unstructured":"Werner-Klein M, Grujovic A, Irlbeck C et al (2020) Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency [J]. Nat Commun 11(1):4977. https:\/\/doi.org\/10.1038\/s41467-020-18701-4","journal-title":"Nat Commun"},{"issue":"1","key":"5843_CR35","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/s41375-019-0493-x","volume":"34","author":"M HO","year":"2020","unstructured":"Ho M, Chen T, Liu J et al (2020) Targeting histone deacetylase 3 (HDAC3) in the bone marrow microenvironment inhibits multiple myeloma proliferation by modulating exosomes and IL-6 trans-signaling [J]. Leukemia 34(1):196\u2013209. https:\/\/doi.org\/10.1038\/s41375-019-0493-x","journal-title":"Leukemia"},{"issue":"3","key":"5843_CR36","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41408-021-00440-4","volume":"11","author":"A VISRAM","year":"2021","unstructured":"Visram A, Dasari S (2021) Relapsed multiple myeloma demonstrates distinct patterns of immune microenvironment and malignant cell-mediated immunosuppression [J]. Blood Cancer J 11(3):45. https:\/\/doi.org\/10.1038\/s41408-021-00440-4","journal-title":"Blood Cancer J"},{"key":"5843_CR37","doi-asserted-by":"publisher","first-page":"704722","DOI":"10.3389\/fonc.2021.704722","volume":"11","author":"M BADROS A Z, MEDDEB","year":"2021","unstructured":"Badros AZ, Meddeb M (2021) Prospective observational study of bisphosphonate-related osteonecrosis of the jaw in multiple myeloma: microbiota profiling and cytokine expression [J]. Front Oncol 11:704722. https:\/\/doi.org\/10.3389\/fonc.2021.704722","journal-title":"Front Oncol"},{"issue":"1","key":"5843_CR38","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1186\/s40001-022-00923-5","volume":"27","author":"M CHEN","year":"2022","unstructured":"Chen M, Zhu J, Yang X et al (2022) PD-1 and LAG-3-positive T cells are associated with clinical outcomes of relapsed\/refractory multiple myeloma patients [J]. Eur J Med Res 27(1):296. https:\/\/doi.org\/10.1186\/s40001-022-00923-5","journal-title":"Eur J Med Res"},{"issue":"11","key":"5843_CR39","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1631\/jzus.B2200277","volume":"23","author":"X YUE","year":"2022","unstructured":"Yue X, Huang L, Yang Y et al (2022) High levels of serum IL-10 indicate disease progression, extramedullary involvement, and poor prognosis in multiple myeloma [J]. J Zhejiang Univ Sci B 23(11):968\u2013974. https:\/\/doi.org\/10.1631\/jzus.B2200277","journal-title":"J Zhejiang Univ Sci B"},{"key":"5843_CR40","doi-asserted-by":"publisher","unstructured":"Nakamura K, Kassem S, Cleynen A et al (2018) Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment [J]. Cancer Cell 33(4):634\u201348 e5. https:\/\/doi.org\/10.1016\/j.ccell.2018.02.007","DOI":"10.1016\/j.ccell.2018.02.007"},{"issue":"1","key":"5843_CR41","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1111\/imm.12061","volume":"139","author":"A BATTAGLIA","year":"2013","unstructured":"Battaglia A, Buzzonetti A, Baranello C et al (2013) Interleukin-21 (IL-21) synergizes with IL-2 to enhance T-cell receptor-induced human T-cell proliferation and counteracts IL-2\/transforming growth factor-beta-induced regulatory T-cell development [J]. Immunology 139(1):109\u2013120. https:\/\/doi.org\/10.1111\/imm.12061","journal-title":"Immunology"},{"issue":"11","key":"5843_CR42","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1016\/j.ejca.2005.12.025","volume":"42","author":"MITSIADES C S","year":"2006","unstructured":"Mitsiades CS, Mitsiades NS, Munshi NC et al (2006) The role of the bone microenvironment in the pathophysiology and therapeutic management of multiple myeloma: interplay of growth factors, their receptors and stromal interactions [J]. Eur J Cancer 42(11):1564\u20131573. https:\/\/doi.org\/10.1016\/j.ejca.2005.12.025","journal-title":"Eur J Cancer"},{"issue":"2","key":"5843_CR43","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1002\/path.4712","volume":"239","author":"J WANG","year":"2016","unstructured":"Wang J, De Veirman K, Faict S et al (2016) Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression [J]. J Pathol 239(2):162\u2013173. https:\/\/doi.org\/10.1002\/path.4712","journal-title":"J Pathol"},{"key":"5843_CR44","unstructured":"Boris Lin KP, Deepak Gupta, Yu-Tzu Tai, Sigui Li, Edie Weller, Teru Hideshima, Suzanne Lentzsch, Faith Davies, Cheng Li, Ellen Weisberg, Schlossman Robert L, Richardson Paul G, James D. Griffin, Jeanette Wood, Nikhil C. Munshi and Kenneth C. Anderson2 (2002) The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787\/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment1 [J]. CANCER RESEARCH"},{"issue":"13","key":"5843_CR45","doi-asserted-by":"publisher","first-page":"6675","DOI":"10.1158\/0008-5472.CAN-06-0190","volume":"66","author":"I TAI Y T, LI X F, BREITKREUTZ","year":"2006","unstructured":"Tai YT, Li XF, Breitkreutz I et al (2006) Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment [J]. Cancer Res 66(13):6675\u20136682. https:\/\/doi.org\/10.1158\/0008-5472.CAN-06-0190","journal-title":"Cancer Res"},{"issue":"8","key":"5843_CR46","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1182\/blood-2011-11-393348","volume":"119","author":"S D\u2019SOUZA","year":"2012","unstructured":"D\u2019souza S, Kurihara N, Shiozawa Y et al (2012) Annexin II interactions with the annexin II receptor enhance multiple myeloma cell adhesion and growth in the bone marrow microenvironment [J]. Blood 119(8):1888\u20131896. https:\/\/doi.org\/10.1182\/blood-2011-11-393348","journal-title":"Blood"},{"issue":"4","key":"5843_CR47","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1111\/j.1365-2141.2011.08864.x","volume":"155","author":"K PODAR","year":"2011","unstructured":"Podar K, Zimmerhackl A, Fulciniti M et al (2011) The selective adhesion molecule inhibitor natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications [J]. Br J Haematol 155(4):438\u2013448. https:\/\/doi.org\/10.1111\/j.1365-2141.2011.08864.x","journal-title":"Br J Haematol"},{"issue":"20","key":"5843_CR48","doi-asserted-by":"publisher","first-page":"3049","DOI":"10.1182\/blood-2014-11-568881","volume":"125","author":"BIANCHI G, MUNSHI N C","year":"2015","unstructured":"Bianchi G, Munshi NC (2015) Pathogenesis beyond the cancer clone(s) in multiple myeloma [J]. Blood 125(20):3049\u20133058. https:\/\/doi.org\/10.1182\/blood-2014-11-568881","journal-title":"Blood"},{"issue":"1","key":"5843_CR49","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41568-021-00413-6","volume":"22","author":"SANCHOE TAURIELLO D V F","year":"2022","unstructured":"Tauriello DVF, Sancho E, Batlle E (2022) Overcoming TGFbeta-mediated immune evasion in cancer [J]. Nat Rev Cancer 22(1):25\u201344. https:\/\/doi.org\/10.1038\/s41568-021-00413-6","journal-title":"Nat Rev Cancer"},{"issue":"7693","key":"5843_CR50","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature25492","volume":"554","author":"D TAURIELLO D V F, PALOMO-PONCE S, ST","year":"2018","unstructured":"Tauriello DVF, Palomo-Ponce S, Stork D et al (2018) TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis [J]. Nature 554(7693):538\u2013543. https:\/\/doi.org\/10.1038\/nature25492","journal-title":"Nature"},{"issue":"2","key":"5843_CR51","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1248\/bpb.b21-00966","volume":"45","author":"T MARUYAMA","year":"2022","unstructured":"Maruyama T, Chen W (2022) TGF-beta and cancer immunotherapy [J]. Biol Pharm Bull 45(2):155\u2013161. https:\/\/doi.org\/10.1248\/bpb.b21-00966","journal-title":"Biol Pharm Bull"},{"issue":"4","key":"5843_CR52","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1111\/j.1365-2141.2005.05860.x","volume":"132","author":"H YASUI","year":"2006","unstructured":"Yasui H, Hideshima T, Richardson PG et al (2006) Novel therapeutic strategies targeting growth factor signalling cascades in multiple myeloma [J]. Br J Haematol 132(4):385\u2013397. https:\/\/doi.org\/10.1111\/j.1365-2141.2005.05860.x","journal-title":"Br J Haematol"},{"key":"5843_CR53","doi-asserted-by":"publisher","unstructured":"Giannakoulas N, Ntanasis-Stathopoulos I, Terpos E (2021) The role of marrow microenvironment in the growth and development of malignant plasma cells in multiple myeloma [J]. Int J Mol Sci 22(9). https:\/\/doi.org\/10.3390\/ijms22094462","DOI":"10.3390\/ijms22094462"},{"key":"5843_CR54","doi-asserted-by":"publisher","unstructured":"Dahmani A, Delisle J-S (2018) TGF-\u03b2 in T Cell biology: implications for cancer immunotherapy [J]. Cancers 10(6). https:\/\/doi.org\/10.3390\/cancers10060194","DOI":"10.3390\/cancers10060194"},{"key":"5843_CR55","doi-asserted-by":"publisher","unstructured":"Bila J, Katodritou E, Guenova M et al (2021) Bone marrow microenvironment interplay and current clinical practice in multiple myeloma: a review of the Balkan myeloma study group [J]. J Clin Med 10(17). https:\/\/doi.org\/10.3390\/jcm10173940","DOI":"10.3390\/jcm10173940"},{"key":"5843_CR56","doi-asserted-by":"publisher","first-page":"1059715","DOI":"10.3389\/fcell.2022.1059715","volume":"10","author":"PS RANA","year":"2022","unstructured":"Rana PS, Soler DC, Kort J et al (2022) Targeting TGF-beta signaling in the multiple myeloma microenvironment: steering CARs and T cells in the right direction [J]. Front Cell Dev Biol 10:1059715. https:\/\/doi.org\/10.3389\/fcell.2022.1059715","journal-title":"Front Cell Dev Biol"},{"key":"5843_CR57","doi-asserted-by":"publisher","unstructured":"Batlle E (2019) Transforming growth factor-beta signaling in immunity and cancer [J]. Immunity 50(4):924\u201340. https:\/\/doi.org\/10.1016\/j.immuni.2019.03.024","DOI":"10.1016\/j.immuni.2019.03.024"},{"issue":"6","key":"5843_CR58","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1016\/j.bone.2008.01.027","volume":"42","author":"M EDWARDS C","year":"2008","unstructured":"Edwards CM, Zhuang J, Mundy GR (2008) The pathogenesis of the bone disease of multiple myeloma [J]. Bone 42(6):1007\u20131013. https:\/\/doi.org\/10.1016\/j.bone.2008.01.027","journal-title":"Bone"},{"issue":"2","key":"5843_CR59","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1007\/BF02989591","volume":"15","author":"MC KYRTSONIS","year":"1998","unstructured":"Kyrtsonis MC, Repa C, Dedoussis GV et al (1998) Serum transforming growth factor-beta 1 is related to the degree of immunoparesis in patients with multiple myeloma [J]. Med Oncol 15(2):124\u2013128. https:\/\/doi.org\/10.1007\/BF02989591","journal-title":"Med Oncol"},{"issue":"12","key":"5843_CR60","doi-asserted-by":"publisher","first-page":"4589","DOI":"10.1182\/blood-2005-10-4169","volume":"107","author":"M DONG","year":"2006","unstructured":"Dong M, Blobe GC (2006) Role of transforming growth factor-beta in hematologic malignancies [J]. Blood 107(12):4589\u20134596. https:\/\/doi.org\/10.1182\/blood-2005-10-4169","journal-title":"Blood"},{"issue":"5","key":"5843_CR61","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1080\/14728222.2020.1744568","volume":"24","author":"C LARSON","year":"2020","unstructured":"Larson C, Oronsky B, Carter C A et al (2020) TGF-beta: a master immune regulator [J]. Expert Opin Ther Targets 24(5):427\u2013438. https:\/\/doi.org\/10.1080\/14728222.2020.1744568","journal-title":"Expert Opin Ther Targets"},{"issue":"2","key":"5843_CR62","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.3892\/ol.2017.6360","volume":"14","author":"X LIU","year":"2017","unstructured":"Liu X, Guo H, Wei Y et al (2017) TGF-beta induces growth suppression in multiple myeloma MM.1S cells via E2F1 [J]. Oncol Lett 14(2):1884\u20131888. https:\/\/doi.org\/10.3892\/ol.2017.6360","journal-title":"Oncol Lett"},{"issue":"12","key":"5843_CR63","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1084\/jem.20021170","volume":"197","author":"CHEN C H","year":"2003","unstructured":"Chen CH, Seguin-Devaux C, Burke NA et al (2003) Transforming growth factor beta blocks Tec kinase phosphorylation, Ca2\u2009+\u2009influx, and NFATc translocation causing inhibition of T cell differentiation [J]. J Exp Med 197(12):1689\u20131699. https:\/\/doi.org\/10.1084\/jem.20021170","journal-title":"J Exp Med"},{"issue":"5","key":"5843_CR64","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.ccr.2005.10.012","volume":"8","author":"J THOMAS D A, MASSAGUE","year":"2005","unstructured":"Thomas DA, Massague J (2005) TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance [J]. Cancer Cell 8(5):369\u2013380. https:\/\/doi.org\/10.1016\/j.ccr.2005.10.012","journal-title":"Cancer Cell"},{"key":"5843_CR65","doi-asserted-by":"publisher","unstructured":"Marchica V, Costa F, Donofrio G et al (2021) Oncolytic virotherapy and microenvironment in multiple myeloma [J]. Int J Mol Sci 22(5). https:\/\/doi.org\/10.3390\/ijms22052259","DOI":"10.3390\/ijms22052259"},{"issue":"2","key":"5843_CR66","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1073\/pnas.0408197102","volume":"102","author":"GORELIKL CHEN M L, PITTET M J","year":"2005","unstructured":"Chen ML, Pittet MJ, Gorelik L et al (2005) Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo [J]. Proc Natl Acad Sci U S A 102(2):419\u2013424. https:\/\/doi.org\/10.1073\/pnas.0408197102","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"5843_CR67","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","volume":"21","author":"D HANAHAN","year":"2012","unstructured":"Hanahan D, Coussens LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment [J]. Cancer Cell 21(3):309\u2013322. https:\/\/doi.org\/10.1016\/j.ccr.2012.02.022","journal-title":"Cancer Cell"},{"issue":"10","key":"5843_CR68","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/nm1001-1118","volume":"7","author":"GORELIKL FLAVELL","year":"2001","unstructured":"Gorelik L, Flavell RA (2001) Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells [J]. Nat Med 7(10):1118\u20131122. https:\/\/doi.org\/10.1038\/nm1001-1118","journal-title":"Nat Med"},{"key":"5843_CR69","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12040817","author":"K SHIMIZU","year":"2020","unstructured":"Shimizu K, Iyoda T, Yamasaki S et al (2020) NK and NKT cell-mediated immune surveillance against hematological malignancies [J]. Cancers (Basel) 12(4). https:\/\/doi.org\/10.3390\/cancers12040817"},{"issue":"7","key":"5843_CR70","doi-asserted-by":"publisher","first-page":"4120","DOI":"10.1073\/pnas.0730640100","volume":"100","author":"R CASTRICONI","year":"2003","unstructured":"Castriconi R, Cantoni C, Della Chiesa M et al (2003) Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells [J]. Proc Natl Acad Sci U S A 100(7):4120\u20134125. https:\/\/doi.org\/10.1073\/pnas.0730640100","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"5843_CR71","doi-asserted-by":"publisher","first-page":"3934","DOI":"10.4049\/jimmunol.1701461","volume":"200","author":"M ZAIATZ-BITTENCOURT V, FINLAY D K, G","year":"2018","unstructured":"Zaiatz-Bittencourt V, Finlay DK, Gardiner CM (2018) Canonical TGF-beta signaling pathway represses human NK cell metabolism [J]. J Immunol 200(12):3934\u20133941. https:\/\/doi.org\/10.4049\/jimmunol.1701461","journal-title":"J Immunol"},{"issue":"1","key":"5843_CR72","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1186\/s12967-021-03165-x","volume":"19","author":"M ZHANG","year":"2021","unstructured":"Zhang M, Jin X, Sun R et al (2021) Optimization of metabolism to improve efficacy during CAR-T cell manufacturing [J]. J Transl Med 19(1):499. https:\/\/doi.org\/10.1186\/s12967-021-03165-x","journal-title":"J Transl Med"},{"key":"5843_CR73","doi-asserted-by":"publisher","unstructured":"Harada T, Hiasa M, Teramachi J et al (2021) Myeloma-bone interaction: a vicious cycle via TAK1-PIM2 signaling [J]. Cancers (Basel) 13(17). https:\/\/doi.org\/10.3390\/cancers13174441","DOI":"10.3390\/cancers13174441"},{"issue":"2","key":"5843_CR74","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.ccell.2022.01.001","volume":"40","author":"S KUMAGAI","year":"2022","unstructured":"Kumagai S, Koyama S, Itahashi K et al (2022) Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments [J]. Cancer Cell 40(2):201\u2013218. https:\/\/doi.org\/10.1016\/j.ccell.2022.01.001","journal-title":"Cancer Cell"},{"issue":"1","key":"5843_CR75","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1080\/15384101.2022.2109105","volume":"22","author":"J XIA","year":"2023","unstructured":"Xia J, Zhang Q, Luan J et al (2023) TGFbeta signaling activation correlates with immune-inflamed tumor microenvironment across human cancers and predicts response to immunotherapy [J]. Cell Cycle 22(1):57\u201372. https:\/\/doi.org\/10.1080\/15384101.2022.2109105","journal-title":"Cell Cycle"},{"issue":"7","key":"5843_CR76","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1038\/s41375-018-0061-9","volume":"32","author":"S XU","year":"2018","unstructured":"Xu S, De Veirman K, De Becker A et al (2018) Mesenchymal stem cells in multiple myeloma: a therapeutical tool or target? [J]. Leukemia 32(7):1500\u20131514. https:\/\/doi.org\/10.1038\/s41375-018-0061-9","journal-title":"Leukemia"},{"key":"5843_CR77","doi-asserted-by":"publisher","unstructured":"Banaszkiewicz M, Malyszko J, Batko K et al (2020) Evaluating the relationship of GDF-15 with clinical characteristics, cardinal features, and survival in multiple myeloma [J]. Mediators Inflamm 2020:5657864. https:\/\/doi.org\/10.1155\/2020\/5657864","DOI":"10.1155\/2020\/5657864"},{"key":"5843_CR78","doi-asserted-by":"publisher","unstructured":"Roy P, Sarkar UA, Basak S (2018) The NF-kappaB activating pathways in multiple myeloma [J]. Biomedicines 6(2). https:\/\/doi.org\/10.3390\/biomedicines6020059","DOI":"10.3390\/biomedicines6020059"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-024-05843-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-024-05843-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-024-05843-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T01:04:26Z","timestamp":1730855066000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-024-05843-4"}},"subtitle":["TGF-\u03b2 in the microenvironment of multiple myeloma"],"short-title":[],"issued":{"date-parts":[[2024,6,20]]},"references-count":78,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["5843"],"URL":"https:\/\/doi.org\/10.1007\/s00277-024-05843-4","relation":{"references":[{"id-type":"uri","id":"","asserted-by":"subject"}]},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,20]]},"assertion":[{"value":"4 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This review didn\u2019t involve personal privacy.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}