{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:28:40Z","timestamp":1789939720568,"version":"4.0.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Regulatory T (Treg) and T helper 17 (Th17) cells play opposing roles in immune responses, and their balance critically regulates the multiple myeloma (MM) microenvironment. Despite advances in immunotherapy, current risk stratification lacks immune biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected the peripheral blood and bone marrow samples from MM patients to investigate the relationships among 1q21 gain\/amplification, the Treg\/Th17 ratio, and <jats:italic>MYC<\/jats:italic> gene abnormalities at diagnosis, remission, and relapse. Additionally, we evaluated the prognostic impact of the Treg\/Th17 ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 130 newly diagnosed MM patients were enrolled, with 82 patients evaluated for 1q21 gain\/amplification. During remission, patients with 1q21 gain\/amplification had a significantly higher Treg\/Th17 ratio (1.59 vs. 0.85, P\u00a0= 0.042) and <jats:italic>MYC<\/jats:italic> expression levels (70.54% vs. 32.76%, P = 0.042) compared to those without 1q21 gain\/amplification. Furthermore, patients with an elevated Treg\/Th17 ratio (&amp;gt;0.7) during remission exhibited slightly higher <jats:italic>MYC<\/jats:italic> expression (45.70% vs. 30.60%) than those with lower ratios (P = 0.451). Patients achieving partial response or better exhibited significantly higher Th17 levels (3.34%, range: 0.19\u201310.80%) at diagnosis compared to those without remission (0.29%, range: 0\u20132.18%, P = 0.033). The group of elevated Treg\/Th17 ratio (&amp;gt; 1.0) at diagnosis exhibited significantly shorter PFS compared to the reduced ratio (\u2264 1.0) group (13.87 months vs. 30.67 months, P = 0.006). R2-ISS staging showed no significant impact on PFS (P = 0.236). By assigning scores to R2-ISS stages and elevated Treg\/Th17 ratio at diagnosis, patients were stratified into low-risk (1\u20133 scores) and high-risk (4\u20135 scores) groups. High-risk patients exhibited significantly worse PFS compared to low-risk patients (P = 0.022). The combined model integrating R2-ISS staging and Treg\/Th17 ratio achieved a concordance index(C-index) of 0.8, surpassing the C-index of R2-ISS staging alone (0.562), demonstrating better predictive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A potential mechanistic connection exists between 1q21 gain\/amplification and immunosuppression, and the role of the <jats:italic>MYC<\/jats:italic> gene in this mechanism has garnered substantial interest. Patients with a higher Treg\/Th17 ratio at diagnosis are more prone to relapse. The combination of R2-ISS staging and the Treg\/Th17 ratio at diagnosis demonstrates stronger predictive ability for relapse.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1595613","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T05:26:07Z","timestamp":1748496367000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Significance of the peripheral blood Treg\/Th17 ratio as a prognostic immune biomarker in newly diagnosed multiple myeloma and its correlation with 1q21 gain\/amplification"],"prefix":"10.3389","volume":"16","author":[{"given":"Jingjing","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaolin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.632564","article-title":"Co-evolution of immune response in multiple myeloma: implications for immune prevention","volume":"12","author":"McCachren","year":"2021","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00333","article-title":"Chemokines modulate immune surveillance in tumorigenesis, metastasis, and response to immunotherapy","volume":"10","author":"Vilgelm","year":"2019","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3600","article-title":"Facts and hopes in multiple myeloma immunotherapy","volume":"27","author":"Sperling","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00347-z","article-title":"Systemic immunity in cancer","volume":"21","author":"Hiam-Galvez","year":"2021","journal-title":"Nat Rev Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13133213","article-title":"Mechanisms of immune evasion in multiple myeloma: open questions and therapeutic opportunities","volume":"13","author":"Botta","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13092018","article-title":"Overcoming the immunosuppressive tumor microenvironment in multiple myeloma","volume":"13","author":"Uckun","year":"2021","journal-title":"Cancers"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/16078454.2023.2288481","article-title":"Activated Tim-3\/Galectin-9 participated in the development of multiple myeloma by negatively regulating CD4 T cells","volume":"29","author":"Zhang","year":"2024","journal-title":"Hematology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1445530","article-title":"Clinical significance of T helper cell subsets in the peripheral blood and bone marrow of patients with multiple myeloma","volume":"15","author":"Zhang","year":"2024","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1714","article-title":"Marrow-infiltrating regulatory T cells correlate with the presence of dysfunctional CD4+PD-1+ Cells and inferior survival in patients with newly diagnosed multiple myeloma","volume":"26","author":"Alrasheed","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179298","article-title":"Deregulated expression of immune checkpoints on circulating CD4 T cells may complicate clinical outcome and response to treatment with checkpoint inhibitors in multiple myeloma patients","volume":"22","author":"Kulikowska De Na\u0142\u0119cz","year":"2021","journal-title":"IJMS"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-014-9980-4","article-title":"The alteration and clinical significance of Th1\/Th2\/Th17\/Treg cells in patients with multiple myeloma","volume":"38","author":"Feng","year":"2015","journal-title":"Inflammation"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ni1261","article-title":"A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17","volume":"6","author":"Park","year":"2005","journal-title":"Nat Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3101","article-title":"Dysfunctional T regulatory cells in multiple myeloma","volume":"107","author":"Prabhala","year":"2006","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07530.x","article-title":"CD4(+)CD25(+)FoxP3(+) regulatory T cells are increased whilst CD3(+)CD4(-)CD8(-)alphabetaTCR(+) Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden","volume":"144","author":"Feyler","year":"2009","journal-title":"Br J Haematol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.575","article-title":"The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterisation of immune status in multiple myeloma","volume":"106","author":"Giannopoulos","year":"2012","journal-title":"Br J Cancer"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-246660","article-title":"Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma","volume":"115","author":"Prabhala","year":"2010","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3742","article-title":"Interleukin 17 is a chief orchestrator of immunity","volume":"18","author":"Veldhoen","year":"2017","journal-title":"Nat Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049446","article-title":"Functionally suppressive CD8 T regulatory cells are increased in patients with multiple myeloma: a cause for immune impairment","volume":"7","author":"Muthu Raja","year":"2012","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.825905","article-title":"Myeloma skews regulatory T and pro-inflammatory T helper 17 cell balance in favor of a suppressive state","volume":"55","author":"Favaloro","year":"2014","journal-title":"Leuk Lymphoma"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.32","article-title":"The cellular immune system in myelomagenesis: NK cells and T cells in the development of myeloma [corrected] and their uses in immunotherapies","volume":"5","author":"Dosani","year":"2015","journal-title":"Blood Cancer J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13020256","article-title":"Gain\/amplification of chromosome arm 1q21 in multiple myeloma","volume":"13","author":"Hanamura","year":"2021","journal-title":"Cancers"},{"key":"B22","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1182\/blood-2020-137060","article-title":"Impact of gain and amplification of 1q in newly diagnosed multiple myeloma patients receiving carfilzomib-based treatment in the forte trial","volume":"136","author":"D\u2019Agostino","year":"2020","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41408-021-00474-8","article-title":"Chromosome 1q21 abnormalities in multiple myeloma","volume":"11","author":"Schmidt","year":"2021","journal-title":"Blood Cancer J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41408-024-00985-0","article-title":"Alterations in chromosome 1q in multiple myeloma randomized clinical trials: a systematic review","volume":"14","author":"Neupane","year":"2024","journal-title":"Blood Cancer J"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-021-04475-2","article-title":"The combination of C-Myc rearrangement and 1q21 gain is associated with poor prognosis in multiple myeloma","volume":"100","author":"Jin","year":"2021","journal-title":"Ann Hematol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2024.101168","article-title":"Chromosomal defects in multiple myeloma","volume":"64","author":"Clarke","year":"2024","journal-title":"Blood Rev"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005885","article-title":"Progression signature underlies clonal evolution and dissemination of multiple myeloma","volume":"137","author":"Shen","year":"2021","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00593-y","article-title":"Single-cell profiling of tumour evolution in multiple myeloma - opportunities for precision medicine","volume":"19","author":"Dutta","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18708","article-title":"Single-cell atlas of the immune microenvironment reveals macrophage reprogramming and the potential dual macrophage-targeted strategy in multiple myeloma","volume":"201","author":"Li","year":"2023","journal-title":"Br J Haematol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0311419","article-title":"MiR-27a inhibits the growth and metastasis of multiple myeloma through regulating Th17\/Treg balance","volume":"19","author":"Lu","year":"2024","journal-title":"PloS One"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1325575","article-title":"Th17\/Treg cell balance in patients with papillary thyroid carcinoma: a new potential biomarker and therapeutic target","volume":"14","author":"Huo","year":"2024","journal-title":"Front Oncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.056176","article-title":"Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders","volume":"97","author":"Ross","year":"2012","journal-title":"Haematologica"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised international staging system for multiple myeloma: A report from international myeloma working group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J Clin Oncol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2017.01.003","article-title":"Therapy for relapsed multiple myeloma: guidelines from the mayo stratification for myeloma and risk-adapted therapy","volume":"92","author":"Dingli","year":"2017","journal-title":"Mayo Clin Proc"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02614","article-title":"Second revision of the international staging system (R2-ISS) for overall survival in multiple myeloma: A european myeloma network (EMN) report within the HARMONY project","volume":"40","author":"D\u2019Agostino","year":"2022","journal-title":"J Clin Oncol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578-1426.2016.02.003","article-title":"The guidelines for the diagnosis and management of multiple myeloma in China (2015 revision): interpretation of initial treatment","volume":"55","author":"Chen","year":"2016","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112138-20200304-00179","article-title":"The guidelines for the diagnosis and management of multiple myeloma in China(2020 revision)","volume":"59","year":"2020","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30206-6","article-title":"International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma","volume":"17","author":"Kumar","year":"2016","journal-title":"Lancet Oncol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-3209","article-title":"Multiomic mapping of acquired chromosome 1 copy-number and structural variants to identify therapeutic vulnerabilities in multiple myeloma","volume":"29","author":"Boyle","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2020.1772473","article-title":"The paradoxical prognostic role of 1q21 Gain\/Amplification in multiple myeloma: every coin has two sides","volume":"61","author":"Xu","year":"2020","journal-title":"Leuk Lymphoma"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2021.1983427","article-title":"Chromosomal 1q21 abnormalities in multiple myeloma: a review of translational, clinical research, and therapeutic strategies","volume":"14","author":"Bisht","year":"2021","journal-title":"Expert Rev Hematol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0132","article-title":"1q21 gain combined with high-risk factors is a heterogeneous prognostic factor in newly diagnosed multiple myeloma: A multicenter study in China","volume":"24","author":"Li","year":"2019","journal-title":"Oncologist"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26639","article-title":"Chromosome 1q21 aberrations identify ultra high-risk myeloma with prognostic and clinical implications","volume":"97","author":"Kastritis","year":"2022","journal-title":"Am J Hematol"},{"key":"B45","article-title":"Predictive value of 1q21 gain in multiple myeloma is strongly dependent on concurrent cytogenetic abnormalities and first-line treatment","volume":"11","author":"Minguela","year":"2021","journal-title":"Am J Cancer Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0220-6","article-title":"Helper T cell differentiation","volume":"16","author":"Saravia","year":"2019","journal-title":"Cell Mol Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/293479","article-title":"The role of regulatory T cells and TH17 cells in multiple myeloma","volume":"2012","author":"Braga","year":"2012","journal-title":"Clin Dev Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"6960","DOI":"10.1038\/s41467-021-26951-z","article-title":"Subclone-specific microenvironmental impact and drug response in refractory multiple myeloma revealed by single-cell transcriptomics","volume":"12","author":"Tirier","year":"2021","journal-title":"Nat Commun"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13020217","article-title":"The role of tumor microenvironment in multiple myeloma development and progression","volume":"13","author":"Garc\u00eda-Ortiz","year":"2021","journal-title":"Cancers"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.53","article-title":"Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma","volume":"25","author":"Chng","year":"2011","journal-title":"Leukemia"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e7194","DOI":"10.1002\/cam4.7194","article-title":"Myc rearrangement redefines the stratification of high-risk multiple myeloma","volume":"13","author":"Jin","year":"2024","journal-title":"Cancer Med"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.136929","article-title":"Concomitant gain of 1q21 and MYC translocation define a poor prognostic subgroup of hyperdiploid multiple myeloma","volume":"101","author":"Weinhold","year":"2016","journal-title":"Haematologica"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061360","article-title":"Role of 1q21 in multiple myeloma: from pathogenesis to possible therapeutic targets","volume":"10","author":"Burroughs Garc\u00eca","year":"2021","journal-title":"Cells"},{"key":"B54","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.ccell.2019.10.001","article-title":"Small-molecule MYC inhibitors suppress tumor growth and enhance immunotherapy","volume":"36","author":"Han","year":"2019","journal-title":"Cancer Cell"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1581529","article-title":"Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1","volume":"8","author":"Pan","year":"2019","journal-title":"Oncoimmunology"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-3513","article-title":"H3K18 lactylation potentiates immune escape of non-small cell lung cancer","volume":"84","author":"Zhang","year":"2024","journal-title":"Cancer Res"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112343","article-title":"IL-17A\/IL-17RA interaction blockade sensitizes synovial macrophages to efferocytosis and PD-L1 signaling via rewiring STAT-3\/ADAM17\/MERTK axis in rheumatoid arthritis animal model","volume":"136","author":"Samarpita","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e31747","article-title":"Combination therapy with probiotics and anti-PD-L1 antibody synergistically ameliorates sepsis in mouse model","volume":"10","author":"Sun","year":"2024","journal-title":"Heliyon"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2019.12.009","article-title":"A unique role of T helper 17 cells in different treatment stages of multiple myeloma","volume":"20","author":"Ma","year":"2020","journal-title":"Clin Lymphoma Myeloma Leukemia"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.19746\/j.cnki.issn.1009-2137.2023.06.024","article-title":"Correlation between peripheral blood PLR with treg, th17 in newly diagnosed multiple myeloma and its influence on prognosis","volume":"31","author":"Qin","year":"2023","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-008-0620-4","article-title":"The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells","volume":"58","author":"Galustian","year":"2009","journal-title":"Cancer Immunol Immunother"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-279893","article-title":"Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma","volume":"116","author":"G\u00f6rg\u00fcn","year":"2010","journal-title":"Blood"},{"key":"B63","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12943-016-0551-1","article-title":"Emerging roles of T helper 17 and regulatory T cells in lung cancer progression and metastasis","volume":"15","author":"Marshall","year":"2016","journal-title":"Mol Cancer"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2013.34","article-title":"Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg\/Th17 balance","volume":"3","author":"Bryant","year":"2013","journal-title":"Blood Cancer J"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0253-2727.2014.12.002","article-title":"Cellular immune function and its clinical implications in 45 patients with multiple myeloma","volume":"35","author":"Zhu","year":"2014","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"B66","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s12026-021-09211-6","article-title":"Recent advances in the role of Th17\/Treg cells in tumor immunity and tumor therapy","volume":"69","author":"Qianmei","year":"2021","journal-title":"Immunol Res"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn121090-20230810-00058","article-title":"Application of the Second Revision of the International Staging System (R2-ISS) in the prognostic assessment of newly diagnosed multiple myeloma","volume":"45","author":"Yan","year":"2024","journal-title":"Zhonghua Xue Ye Xue Za Zhi"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1595613\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T05:26:11Z","timestamp":1748496371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1595613\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":67,"alternative-id":["10.3389\/fimmu.2025.1595613"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1595613","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,29]]},"article-number":"1595613"}}