Blood Cancer Journal最新文献

{"title":"Clinical characteristics and outcomes of 476 mantle cell lymphoma patients aged 80 years and older","authors":"Simon Pahnke, Kossi D. Abalo, Sara Ekberg, Alexandra Albertsson-Lindblad, Karin E. Smedby, Mats Jerkeman, Ingrid Glimelius","doi":"10.1038/s41408-024-01204-6","DOIUrl":"https://doi.org/10.1038/s41408-024-01204-6","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"8 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded tumor-associated polymorphonuclear myeloid-derived suppressor cells in Waldenstrom macroglobulinemia display immune suppressive activity","authors":"Vaishali Bhardwaj, Zhi-Zhang Yang, Shahrzad Jalali, Jose C. Villasboas, Rekha Mudappathi, Junwen Wang, Prithviraj Mukherjee, Jonas Paludo, Xinyi Tang, Hyo Jin Kim, Jordan E. Krull, Kerstin Wenzl, Anne J. Novak, Patrizia Mondello, Stephen M. Ansell","doi":"10.1038/s41408-024-01173-w","DOIUrl":"https://doi.org/10.1038/s41408-024-01173-w","url":null,"abstract":"<p>The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains poorly understood. Here we transcriptionally and phenotypically profiled non-malignant (CD19^- CD138^-) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper understanding of their role in WM. We found that HLA-DR^lowCD11b⁺CD33⁺ MDSCs were significantly increased in WM patients as compared to normal controls, with an expansion of predominantly polymorphonuclear (PMN)-MDSCs. Single-cell immunogenomic profiling of WM MDSCs identified an immune-suppressive gene signature with upregulated inflammatory pathways associated with interferon and tumor necrosis factor (TNF) signaling. Gene signatures associated with an inflammatory and immune suppressive environment were predominately expressed in PMN-MDSCs. In vitro, WM PMN-MDSCs demonstrated robust T-cell suppression and their viability and expansion was notably enhanced by granulocyte colony stimulating factor (G-CSF) and TNFα. Furthermore, BM malignant B-cells attracted PMN-MDSCs to a greater degree than monocytic MDSCs. Collectively, these data suggest that malignant WM B cells actively recruit PMN-MDSCs which promote an immunosuppressive BM microenvironment through a direct T cell inhibition, while release of G-CSF/TNFα in the microenvironment further promotes PMN-MDSC expansion and in turn immune suppression. Targeting PMN-MDSCs may therefore represent a potential therapeutic strategy in patients with WM.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"42 2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The significance of free light-chain ratio in light-chain monoclonal gammopathy of undetermined significance: a flow cytometry sub-study of the iStopMM screening study","authors":"Jón Þórir Óskarsson, Sæmundur Rögnvaldsson, Sigrun Thorsteinsdottir, Thorir Einarsson Long, Andri Ólafsson, Elias Eythorsson, Ásbjörn Jónsson, Brynjar Viðarsson, Páll T. Önundarson, Bjarni A. Agnarsson, Róbert Pálmason, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Stephen J. Harding, Brian G. M. Durie, Thorvardur Jon Love, Sigurdur Y. Kristinsson","doi":"10.1038/s41408-024-01201-9","DOIUrl":"https://doi.org/10.1038/s41408-024-01201-9","url":null,"abstract":"<p>Light-chain (LC) monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. LC-MGUS is characterized by free light-chain (FLC) levels outside defined reference intervals, indirectly indicating underlying plasma cell (PC) monoclonality. Next-generation flow cytometry (NGF) was used to evaluate clonal PC presence in bone marrow (BM) samples from individuals with LC-MGUS in the iStopMM study, aiming to assess the predictive value of the FLC ratio for clonal PC presence and its prognostic implications. BM samples from 61 individuals with LC monoclonal gammopathy were analyzed. Clonal plasma cells were detected in 53.6% of LC-MGUS samples (<i>n</i> = 28) and in all samples from individuals with more advanced conditions (<i>n</i> = 33). The FLC ratio was predictive of clonal PC presence for kappa-involved FLC ratios (<i>p</i> &lt; 0.05; <i>n</i> = 42), with an optimal cutoff of 3.15 (96.7% sensitivity, 91.7% specificity). Of 195 individuals with kappa-involved LC-MGUS in follow-up within the iStopMM study, none with FLC ratios &gt;1.65 to 3.15 progressed to MM (<i>n</i> = 124), whereas 4/71 (5.6%) with FLC ratios &gt;3.15 progressed over median follow-up of 55 months. These findings support using a kappa-involved FLC ratio cutoff of &gt;3.15 to more accurately identify individuals at increased risk of developing symptomatic PC disorders.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"77 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study","authors":"Yi Zhang, Hu Zhou, Shanshan Suo, Junling Zhuang, Linhua Yang, Aili He, Qingchi Liu, Xin Du, Sujun Gao, Yarong Li, Yan Li, Yuqing Chen, Wen Wu, Huanling Zhu, Guangsheng He, Mei Hong, Qian Jiang, Zhongxing Jiang, Hongmei Jing, Jishi Wang, Na Xu, Lingling Yue, Cuiping Zheng, Zeping Zhou, Chenghao Jin, Xin Li, Lin Liu, Yajing Xu, Dengshu Wu, Feng Zhang, Jin Zhang, Liqing Wu, Hewen Yin, Binhua Lv, Zhijian Xiao, Jie Jin","doi":"10.1038/s41408-024-01202-8","DOIUrl":"https://doi.org/10.1038/s41408-024-01202-8","url":null,"abstract":"<p>To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), <i>P</i> = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, <i>P</i> &lt; 0.0001. The TSS50 rates were 62.0% for gecacitinib- and 50% for HU-treated patients. Among non-transfusion-dependent patients with baseline hemoglobin (HGB) ≤ 100 g/L, 31.0% (13/42) in the gecacitinib group showed a ≥20 g/L increase in HGB, compared to 15.0% (3/20) in HU group. The common grade ≥ 3 treatment-emergent adverse events (TEAEs), including anemia (26.8% vs 44.1%), thrombocytopenia (15.5% vs 32.4%), leukopenia (2.8% vs 20.6%), and neutropenia (1.4% vs 20.6%), were less frequent with gecacitinib than HU. Treatment discontinuation due to TEAEs was lower in gecacitinib (7.0%) compared to HU (11.8%). Gecacitinib demonstrates superior efficacy and a more favorable safety profile compared to HU, making it a promising treatment option for managing MF, particularly in patients with anemia (This trial was registered with ClinicalTrials.gov, (NCT04617028)).</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"13 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elranatamab monotherapy in the real-word setting in relapsed-refractory multiple myeloma: results of the French compassionate use program on behalf of the IFM","authors":"Florent Malard, Arthur Bobin, Myriam Labopin, Lionel Karlin, Laurent Frenzel, Murielle Roussel, Marguerite Vignon, Sophie Godet, Thomas Chalopin, Perrine Moyer, Emilie Chalayer, Frederique Orsini Piocelle, Clara Mariette, Carolyne Croizier, Claudine Sohn, Mamoun Dib, Ronan Le Calloch, Nadia Ali-Ammar, Marion Loirat, Omar Benbrahim, Alexandre Payssot, Adrien Trebouet, Aurore Perrot, Xavier Leleu, Mohamad Mohty","doi":"10.1038/s41408-024-01200-w","DOIUrl":"https://doi.org/10.1038/s41408-024-01200-w","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"64 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic and spatial analysis reveal the immunosuppressive microenvironment in relapsed/refractory angioimmunoblastic T-cell lymphoma","authors":"Mengyan Zhu, Ning Li, Lei Fan, Rongrong Wu, Lei Cao, Yimin Ren, Chuanyang Lu, Lishen Zhang, Yun Cai, Yuzhu Shi, Zihan Lin, Xueying Lu, Jiayan Leng, Shiyang Zhong, Xingfei Hu, Bin Huang, Runheng Huang, Wanting Zhou, Diru Yao, Lingxiang Wu, Wei Wu, Quanzhong Liu, Peng Xia, Ruize Chen, Wenyu Shi, Ruohan Zhang, Sali Lv, Chunling Wang, Liang Yu, Jianyong Li, Qianghu Wang, Kening Li, Hui Jin","doi":"10.1038/s41408-024-01199-0","DOIUrl":"https://doi.org/10.1038/s41408-024-01199-0","url":null,"abstract":"<p>Angioimmunoblastic T-cell lymphoma (AITL) is a kind of aggressive T-cell lymphoma with significant enrichment of non-malignant tumor microenvironment (TME) cells. However, the complexity of TME in AITL progression is poorly understood. We performed single-cell RNA-Seq (scRNA-seq) and imaging mass cytometry (IMC) analysis to compare the cellular composition and spatial architecture between relapsed/refractory AITL (RR-AITL) and newly diagnosed AITL (ND-AITL). Our results showed that the malignant T follicular helper (Tfh) cells showed significantly increased proliferation driven by transcriptional activation of YY1 in RR-AITL, which is markedly associated with the poor prognosis of AITL patients. The CD8⁺ T cell proportion and cytotoxicity decreased in RR-AITL TME, resulting from elevated expression of the inhibitory checkpoints such as PD-1, TIGIT, and CTLA4. Notably, the transcriptional pattern of B cells in RR-AITL showed an intermediate state of malignant transformation to B-cell-lymphoma, and contributed to immune evasion by highly expressing CD47 and PD-L1. Besides, compared to ND-AITL samples, myeloid-cells-centered spatial communities were more prevalent but showed reduced phagocytic activity and impaired antigen processing and presentation in RR-AITL TME. Furthermore, specific inhibitory ligand-receptor interactions, such as <i>CLEC2D</i>-<i>KLRB1</i>, <i>CTLA4</i>-<i>CD86</i>, and <i>MIF</i>-<i>CD74</i>, were exclusively identified in the RR-AITL TME. Our study provides a high-resolution characterization of the immunosuppression ecosystem and reveals the potential therapeutic targets for RR-AITL patients.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"47 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic clustering of chronic lymphocytic leukemia: molecular subtypes based on Bruton’s tyrosine kinase expression levels","authors":"Gorkem Kismali, Ganiraju Manyam, Nitin Jain, Cristina Ivan, Betty Lamothe, Mary L. Ayres, LaKesla R. Iles, William G. Wierda, Varsha Gandhi","doi":"10.1038/s41408-024-01196-3","DOIUrl":"https://doi.org/10.1038/s41408-024-01196-3","url":null,"abstract":"<p>Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression. We hypothesized that transcriptome and proteome may identify functional omics associated with CLL nosology. As a test cohort, we utilized publicly available treatment-naïve CLL transcriptomics data (<i>n</i> = 130) and did consensus clustering that identified BTK-expression-based clusters. The BTK-High and BTK-Low clusters were validated in public and our in-house databases (<i>n</i> = &gt;550 CLL patients). To associate with functional relevance, we took samples from 151 previously treated patient with CLL and analyzed them using RNA sequencing and reverse-phase protein array. Transcript levels were strongly correlated with BTK protein levels. BTK-High subtype showed increased CCL3/CCL4 levels and disease burden such as high WBC. BTK-Low subtype showed down-regulated mRNA/proteins of DNA-repair pathway and increased DNA-damage-response, which may have contributed to enrichment of inflammatory pathway. BTK-Low subtype was rich in proapoptotic gene and protein expression and relied less on BCR pathway. High-BTK subgroup was enriched in replication/repair pathway and transcription machinery. In conclusion, profiling of 5 datasets of ~700 patients revealed unique BTK-associated expression clusters in CLL.</p><figure></figure>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"22 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy","authors":"Maximilian Merz, Danai Dima, Hamza Hashmi, Nausheen Ahmed, Friedrich Stölzel, Tobias A. W. Holderried, Roland Fenk, Fabian Müller, Natalia Tovar, Aina Oliver-Cáldes, Kristin Rathje, James A. Davis, David Fandrei, Vladan Vucinic, Soraya Kharboutli, Ben-Niklas Baermann, Francis Ayuk, Uwe Platzbecker, Anca-Maria Albici, Nathalie Schub, Friederike Schmitz, Leyla Shune, Jack Khouri, Faiz Anwer, Shahzad Raza, Joseph McGuirk, Zahra Mahmoudjafari, Kimberly Green, Cyrus Khandanpour, Marcel Teichert, Barbara Jeker, Michele Hoffmann, Nicolaus Kröger, Bastian von Tresckow, Carlos Fernández de Larrea, Thomas Pabst, Al-Ola Abdallah, Nico Gagelmann","doi":"10.1038/s41408-024-01197-2","DOIUrl":"https://doi.org/10.1038/s41408-024-01197-2","url":null,"abstract":"<p>Despite the astonishing outcomes after chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory multiple myeloma (RRMM), most patients eventually relapse. There are only limited data available on salvage therapies following relapse after BCMA-directed CAR T-cell therapy. Here, we analyzed outcomes of post-CAR T-cell therapy relapse and impact of different salvage strategies in an international cohort of 139 patients (<i>n</i> = 130 ide-cel, <i>n</i> = 9 cilta-cel), receiving talquetamab (<i>n</i> = 28), teclistamab (<i>n</i> = 37), combinations of immunomodulating drugs (IMiDs), proteasome inhibitors (PIs) or CD38 monoclonal antibodies (<i>n</i> = 43), and others (<i>n</i> = 31). The median time to relapse after CAR T-cell therapy was 5 months, 53% had the extramedullary disease (EMD) at relapse, associated with dismal post-relapse outcome (<i>P</i> = 0.005). Overall response and complete response upon salvage therapies were 79% and 39% for talquetamab, 64% and 32% for teclistamab, 30% and 0% for IMiDs/PIs/CD38, and 26% and 3% for others (<i>P</i> &lt; 0.001). Duration of response, as well as median survival, was significantly improved with bispecific antibodies (<i>P</i> &lt; 0.001, respectively). Bispecific antibodies seemed to overcome the poor prognosis associated with early relapse and EMD, and were independent predictors for improved survival in multivariable analysis. In summary, these results suggest bispecific antibodies as the standard of care for relapse after CAR T-cell therapy for RRMM.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"27 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world characteristics and outcomes of patients with high-risk and non-high-risk smoldering multiple myeloma using the Flatiron Health database","authors":"S. Vincent Rajkumar, María-Victoria Mateos, Marcy Schaeffer, Xiwu Lin, Sacheeta Bathija, Niodita Gupta-Werner, Annette Lam, Robin Carson, Robyn Dennis, Shuchita Kaila, Kathryn Matt, Joana Duran, Sagar Lonial","doi":"10.1038/s41408-024-01170-z","DOIUrl":"https://doi.org/10.1038/s41408-024-01170-z","url":null,"abstract":"<p>This study aimed to provide real-world evidence on progression risk in patients with high-risk smoldering multiple myeloma (SMM). This retrospective, observational study leveraged data from the Flatiron Health database. Eligible patients had SMM and relevant measures to apply Mayo 2018, International Myeloma Working Group (IMWG) 2020, and AQUILA trial risk criteria. Time to progression to active MM (TTP), progression or death (PFS), and death or progression on first-line MM therapy (PFS2) were evaluated using Kaplan–Meier methods and multivariate Cox regression models adjusted for age, Charlson Comorbidity Index, and time from SMM diagnosis to risk classification date. Across the three risk models (Mayo 2018, IMWG 2020, and AQUILA trial), high-risk patients with SMM had 3.0–4.0 times the risk of TTP, 2.1–3.5 times the risk of PFS, and 1.7–3.2 times the risk of PFS2 versus non-high-risk patients (<i>p</i> &lt; 0.001 for all comparisons). Similar results were observed when patients with early treatment, early progression, and/or bone disease were excluded. This study demonstrates that high-risk patients with SMM have worse prognoses than non-high-risk patients, regardless of the criteria used, and highlights a need for early intervention testing.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"23 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies","authors":"Zhongfei Tao, Zuzana Chyra, Jana Kotulová, Piotr Celichowski, Jana Mihályová, Sandra Charvátová, Roman Hájek","doi":"10.1038/s41408-024-01193-6","DOIUrl":"https://doi.org/10.1038/s41408-024-01193-6","url":null,"abstract":"<p>Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigms for hematological malignancies. However, more than half of these patients cannot achieve sustainable tumor control, partially due to the inadequate potency of CAR-T cells in eradicating tumor cells. T cells are crucial components of the anti-tumor immune response, and multiple intrinsic T-cell features significantly influence the outcomes of CAR-T cell therapy. Herein, we review progressing research on T-cell characteristics that impact the effectiveness of CAR-T cells, including T-cell exhaustion, memory subsets, senescence, regulatory T-cells, the CD4⁺ to CD8⁺ T-cell ratio, metabolism, and the T-cell receptor repertoire. With comprehensive insight into the biological processes underlying successful CAR-T cell therapy, we will further refine the applications of these novel therapeutic modalities, and enhance their efficacy and safety for patients.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"129 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}