Journal of Hematology & Oncology最新文献

{"title":"Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy","authors":"Qin Hu, Yifei Zhu, Jie Mei, Ying Liu, Guoren Zhou","doi":"10.1186/s13045-025-01717-y","DOIUrl":"https://doi.org/10.1186/s13045-025-01717-y","url":null,"abstract":"The extracellular matrix (ECM), closely linked to the dynamic changes in the tumor microenvironment (TME), plays a critical role in modulating tumor immunity. The dual role of the ECM in tumor progression, encompassing both promotion and inhibition, is attributed to its components influencing immune cell activation, migration, and infiltration. This mechanism is intricately connected with the efficacy of immunotherapies. Currently, there is limited understanding of how ECM remodeling spatially and temporally coordinates with immune checkpoint inhibitors (ICIs) or adoptive cell therapies. Furthermore, strategies to selectively target pathological ECM components while preserving their homeostatic functions urgently require systematic investigation. In this review, we summarize current findings on the interplay between ECM and tumor immune regulation, with a particular focus on how key ECM components contribute to immune modulation. Furthermore, we discuss emerging strategies targeting ECM-related mechanisms to enhance the efficacy of immunotherapies, including approaches that remodel the ECM to improve immune infiltration and strategies that synergize with existing immunotherapies. By integrating these insights, we provide a perspective on leveraging ECM-targeted interventions to overcome immune evasion and optimize cancer immunotherapy outcomes.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"30 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319753","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":"Menin inhibitors from monotherapies to combination therapies: clinical trial updates from 2024 ASH annual meeting","authors":"Gejia Cao, Haixiao Zhang, Shu Sun, Hong-Hu Zhu","doi":"10.1186/s13045-025-01718-x","DOIUrl":"https://doi.org/10.1186/s13045-025-01718-x","url":null,"abstract":"Menin inhibitors, which target the KMT2A-menin protein-protein interaction to inhibit blasts proliferation and induce differentiation, have demonstrated potential effects on acute leukemia subtypes characterized by overexpression of HOXA gene cluster and MEIS1 (including KMT2A rearrangements, NPM1 mutations, NUP98 rearrangements and other genetic alterations). Following the promising outcomes of the two pioneering menin inhibitors, revumenib and ziftomenib, other menin inhibitors, including bleximenib, enzomenib, BN-104 and HMPL-506 are currently under investigation in clinical trials. Several trials presented their initial outcomes at the 2024 ASH Annual Meeting. This review highlights the key outcomes of these pivotal clinical trials.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304719","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":"Correction: Ube2v1-mediated ubiquitination and degradation of Sirt1 promotes metastasis of colorectal cancer by epigenetically suppressing autophagy","authors":"Tong Shen, Ling-Dong Cai, Yu-Hong Liu, Shi Li, Wen-Juan Gan, Xiu-Ming Li, Jing-Ru Wang, Peng-Da Guo, Qun Zhou, Xing-Xing Lu, Li-Na Sun, Jian-Ming Li","doi":"10.1186/s13045-025-01719-w","DOIUrl":"https://doi.org/10.1186/s13045-025-01719-w","url":null,"abstract":"<p><b>Correction to: Journal of Hematology &amp; Oncology (2018) 11:95.</b></p><p><b>https://doi.org/10.1186/s13045-018-0638-9</b></p><p>During figure preparation, an incorrect representative image was included in Figs. 1e, S5B, and S6C. These errors occurred during figure assembly and do not affect the results or conclusions of the study. The corrected figures have been provided.</p><p>The authors apologize for the errors and any confusion caused.</p><p>Fig. 1e</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01719-w/MediaObjects/13045_2025_1719_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"363\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01719-w/MediaObjects/13045_2025_1719_Fig1_HTML.png\" width=\"685\"/></picture></figure><p>Fig. S5B</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01719-w/MediaObjects/13045_2025_1719_Fig2_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 2\" aria-describedby=\"Fig2\" height=\"561\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01719-w/MediaObjects/13045_2025_1719_Fig2_HTML.png\" width=\"685\"/></picture></figure><p>Fig. S5B/C</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01719-w/MediaObjects/13045_2025_1719_Fig3_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 3\" aria-describedby=\"Fig3\" height=\"444\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01719-w/MediaObjects/13045_2025_1719_Fig3_HTML.png\" width=\"685\"/></picture></figure><span>Author notes</span><ol><li><p>Tong Shen, Ling-Dong Cai and Yu-Hong Liu contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Department of Pathology, Soochow University Medical School, Suzhou, 215123, People’s Republic of China</p><p>Tong Shen, Ling-Dong Cai, Shi Li, Wen-Juan Gan, Xiu-Ming Li, Jing-Ru Wang, Peng-Da Guo, Qun Zhou, Xing-Xing Lu, Li-Na Sun &amp; Jian-Ming Li</p></li><li><p>Department of Pathology, Baoan Hospital, Southern Medical University, Shenzhen, 518101, People’s Republic of China</p><p>Yu-Hong Liu</p></li></ol><span>Authors</span><ol><li><span>Tong Shen</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Ling-Dong Cai</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Yu-Hong Liu</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Shi Li</span>View author publications<p><span>You can also search for this author in</sp","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"598 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304702","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":"Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects","authors":"Hongzhuo Qin, Zhaokai Zhou, Run Shi, Yumiao Mai, Yudi Xu, Fu Peng, Guangyang Cheng, Pengpeng Zhang, Wenjie Chen, Yun Chen, Yajun Chen, Ran Xu, Qiong Lu","doi":"10.1186/s13045-025-01701-6","DOIUrl":"https://doi.org/10.1186/s13045-025-01701-6","url":null,"abstract":"Immunotherapy has revolutionized the oncology treatment paradigm, and CAR-T cell therapy in particular represents a significant milestone in treating hematological malignancies. Nevertheless, tumor resistance due to target heterogeneity or mutation remains a Gordian knot for immunotherapy. This review elucidates molecular mechanisms and therapeutic potential of next-generation immunotherapeutic tools spanning genetically engineered immune cells, multi-specific antibodies, and cell engagers, emphasizing multi-targeting strategies to enhance personalized immunotherapy efficacy. Development of logic gate modulation-based circuits, adapter-mediated CARs, multi-specific antibodies, and cell engagers could minimize adverse effects while recognizing tumor signals. Ultimately, we highlight gene delivery, gene editing, and other technologies facilitating tailored immunotherapy, and discuss the promising prospects of artificial intelligence in gene-edited immune cells.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"250 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237338","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":"Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies","authors":"Quchang Ouyang, Jordi Rodon, Yan Liang, Xinhong Wu, Qun Li, Lihua Song, Min Yan, Zhongsheng Tong, YunPeng Liu, Zev A. Wainberg, Ying Wang, Cuizhi Geng, Susanna V. Ulahannan, Guohua Yu, Manish R. Sharma, Xiang Wang, Judy S. Wang, Alexander Spira, Weihong Zhao, Rachel E. Sanborn, Ying Cheng, Xian Wang, Gesha Liu, Yaling Li, Junyou Ge, Elliot Chartash, Omobolaji O. Akala, Yongmei Yin","doi":"10.1186/s13045-025-01705-2","DOIUrl":"https://doi.org/10.1186/s13045-025-01705-2","url":null,"abstract":"Sacituzumab tirumotecan (sac-TMT) is an antibody–drug conjugate composed of an anti-TROP2 monoclonal antibody coupled to a cytotoxic belotecan-derived topoisomerase I inhibitor (KL610023) via a novel linker. We report results from the phase 1 dose-escalation cohorts in advanced solid tumors and phase 2 expansion cohorts for metastatic triple-negative breast cancer (TNBC) from the first-in-human MK-2870-001 (KL264-01) study (NCT04152499). Patients had unresectable locally advanced/metastatic solid tumors refractory to standard therapies. In the phase 1 dose-escalation cohorts, patients had unresectable locally advanced/metastatic solid tumors refractory to standard therapies. Sac-TMT was administered by intravenous administration every 2 weeks at 2 to 12 mg/kg. In phase 2, patients with TNBC and HR+/HER2− breast cancer received sac-TMT per recommended doses for expansion (RDEs) identified in phase 1. Primary objectives were determining maximum tolerated dose (MTD) of sac-TMT and establishing RDEs (phase 1) and determining ORR per RECIST v1.1 by investigator assessment (phase 2). Adverse events were assessed per NCI-CTCAE version 5.0. Thirty patients were enrolled in phase 1 and received sac-TMT 2 mg/kg (n = 4), 4 mg/kg (n = 7), 5 mg/kg (n = 7), 5.5 mg/kg (n = 5), and 6 mg/kg (n = 7). Five patients had dose-limiting toxicities: grade 3 stomatitis at 4, 5.5, and 6 mg/kg; grade 3 rash at 5 mg/kg; and grade 3 urticaria at 6 mg/kg. MTD was 5.5 mg/kg and RDEs were 4 and 5 mg/kg. In the phase 2 dose expansion, ORR (95% CI) was 34.8% (16.4%, 57.3%) in the 4-mg/kg group (n = 23) and 38.9% (23.1%, 56.5%) in the 5-mg/kg group (n = 36) for TNBC. ORR (95% CI) was 31.7% (18.1%, 48.1%) for HR+/HER2− breast cancer (n = 41). Sac-TMT demonstrated manageable safety profile in patients with unresectable locally advanced/metastatic solid tumors and promising antitumor activity in metastatic TNBC and HR+/HER2 − breast cancer. Sac-TMT is being investigated in phase 3 studies. ClinicalTrials.gov, NCT04152499.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"36 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228900","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":"Correction: BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial","authors":"Hao Yao, Shi-hui Ren, Lin-hui Wang, Ming-qiang Ren, Jiao Cai, Dan Chen, Ying He, Si-han Lai, Bai-tao Dou, Meng-jiao Li, Yan-ling Li, Ya-li Cen, Alex H. Chang, Yi Su, Ling Qiu, Fang-yi Fan","doi":"10.1186/s13045-025-01714-1","DOIUrl":"https://doi.org/10.1186/s13045-025-01714-1","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Journal of Hematology &amp; Oncology (2025) 18:56&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s13045-025-01713-2&lt;/b&gt;&lt;/p&gt;&lt;p&gt;The original article has been corrected to restore co-authors Yi Su, Ling Qiu, and Fang-yi Fan (lead contact) to co-Corresponding Authorship which was mistakenly removed by the production team which handled this article.&lt;/p&gt;&lt;span&gt;Author notes&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Hao Yao, Shi-hui Ren, Lin-hui Wang and Ming-qiang Ren contributed equally to this work.&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Department of Hematology, Chinese People’s Liberation Army The General Hospital of Western Theater Command, Chengdu, 610083, Sichuan, China&lt;/p&gt;&lt;p&gt;Hao Yao, Shi-hui Ren, Jiao Cai, Dan Chen, Ying He, Si-han Lai, Bai-tao Dou, Meng-jiao Li, Yan-ling Li, Ya-li Cen, Yi Su, Ling Qiu &amp; Fang-yi Fan&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Branch of National Clinical Research Center for Hematological Disease, Chengdu, 610083, Sichuan, China&lt;/p&gt;&lt;p&gt;Hao Yao, Shi-hui Ren, Jiao Cai, Dan Chen, Ying He, Si-han Lai, Bai-tao Dou, Meng-jiao Li, Yan-ling Li, Ya-li Cen, Yi Su, Ling Qiu &amp; Fang-yi Fan&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Sichuan Clinical Research Center for Hematological Disease, Chengdu, 610083, China&lt;/p&gt;&lt;p&gt;Hao Yao, Shi-hui Ren, Jiao Cai, Dan Chen, Ying He, Si-han Lai, Bai-tao Dou, Meng-jiao Li, Yan-ling Li, Ya-li Cen, Yi Su, Ling Qiu &amp; Fang-yi Fan&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, Sichuan, China&lt;/p&gt;&lt;p&gt;Bai-tao Dou, Meng-jiao Li, Yan-ling Li &amp; Fang-yi Fan&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Institute of Basic Medicine, North Sichuan Medical College, Nanchong, 637000, Sichuan, China&lt;/p&gt;&lt;p&gt;Hao Yao&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Hematology, The People’s Hospital of Guizhou Province, Guiyang, 550002, Guizhou, China&lt;/p&gt;&lt;p&gt;Lin-hui Wang&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Hematology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou Province, China&lt;/p&gt;&lt;p&gt;Ming-qiang Ren&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200438, China&lt;/p&gt;&lt;p&gt;Alex H. Chang&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Shanghai YaKe Biotechnology Ltd., Yangpu District, Shanghai, 200090, China&lt;/p&gt;&lt;p&gt;Alex H. Chang&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Hao Yao&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;You can also search for this author in&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Shi-hui Ren&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;You can also search for this author in&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Lin-hui Wang&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;You can also search for this author in&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Ming-qiang Ren&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;You can also search for this author in&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Jiao Cai&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;You can also search for ","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"102 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211126","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":"Integrated clinical and proteomic-based model for diagnostic and prognostic prediction in pRCC","authors":"Zeya Xu, Linhui Zhang, Jiacheng Lyu, Maoping Cai, Tao Ji, Lin Bai, Liqing Li, Yao Zhu, Huashan Xu, Subei Tan, Hualei Gan, Shujuan Ni, Wenhao Xu, Xi Tian, Aihetaimujiang Anwaier, Beiyan Liu, Qinqin Hou, Guohai Shi, Hailiang Zhang, Jianyuan Zhao, Dingwei Ye, Yuanyuan Qu, Chen Ding","doi":"10.1186/s13045-025-01707-0","DOIUrl":"https://doi.org/10.1186/s13045-025-01707-0","url":null,"abstract":"Papillary renal cell carcinoma (pRCC), a main pathological subtype of non-clear cell RCC (nccRCC), has strong heterogeneity. Comparing to other nccRCC subtypes, advanced pRCC has the poorest prognosis. Due to its lower incidence compared to ccRCC, clinical research and exploration of non-invasive biomarkers for pRCC are limited, and it is often misclassified. Herein, we leveraged the advantages of non-invasive plasma samples and the extensive coverage of mass spectrometry (MS)-based proteomics to develop a series of predictive models. First, we established the RCC subtype diagnostic model, which accurately differentiates pRCC, ccRCC, chromophobe RCC (chRCC), and healthy controls, achieving robust performance with an area under the receiver operating characteristic curve (AUROC) of 0.96 and averaged precision (AP) score of 0.91. Furthermore, recognizing the pivotal role of TNM staging in pRCC clinical management, we developed the the TNM staging diagnostic model with AUROC was 0.92 as the complementary noninvasive strategy. Finally, to facilitate real-time clinical monitoring of progression-free survival (PFS), we integrated routine blood indicators and proteomic features to develop the time-clock progression model, which demonstrated high predictive performance (AUROC > 0.95, AP > 0.95). In summary, this study provides a comprehensive plasma proteomic analysis and establishes diagnostic and prognostic predictive models for pRCC.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"36 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165414","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":"Panoramic spatial enhanced resolution proteomics (PSERP) reveals tumor architecture and heterogeneity in gliomas","authors":"Ziyan Xu, Yunzhi Wang, Tao Xie, Rongkui Luo, Heng-Li Ni, Hang Xiang, Shaoshuai Tang, Subei Tan, Rundong Fang, Peng Ran, Qiao Zhang, Xiaomeng Xu, Sha Tian, Fuchu He, Wenjun Yang, Chen Ding","doi":"10.1186/s13045-025-01710-5","DOIUrl":"https://doi.org/10.1186/s13045-025-01710-5","url":null,"abstract":"The spatial proteomic profiling of complex tissues is essential for investigating cellular function in physiological and pathological states. However, the imbalance among resolution, protein coverage, and expense precludes their systematic application to analyze whole tissue sections in an unbiased manner and with high resolution. Here, we introduce panoramic spatial enhanced resolution proteomics (PSERP), a method that combines tissue expansion, automated sample segmentation, and tryptic digestion with high-throughput proteomic profiling. The PSERP approach facilitates rapid quantitative profiling of proteomic spatial variability in whole tissue sections at sub-millimeter resolution. We demonstrated the utility of this method for determining the streamlined large-scale spatial proteomic features of gliomas. Specifically, we profiled spatial proteomic features for nine glioma samples across three different mutation types (IDH1-WT/EGFR-mutant, IDH1-mutant, and IDH1/EGFR-double-WT gliomas) at sub-millimeter resolution (corresponding to a total of 2,230 voxels). The results revealed over 10,000 proteins identified in a single slide, which helps us to portray the diverse proteins and pathways with spatial abundance patterns in the context of tumor heterogeneity and cellular features. Our spatial proteomic data revealed distinctive proteomic features of malignant and non-malignant tumor regions and depicted the distribution of proteins from tumor centers to tumor borders and non-malignant tumor regions. Through integrative analysis with single-cell transcriptomic data, we elucidated the cellular composition and cell–cell communications in a spatial context. Our PSERP also includes a spatially resolved tumor-specific peptidome identification workflow that not only enables us to elucidate the spatial expression patterns of tumor-specific peptides in glioma samples with different genomic types but also provides us with opportunities to select combinations of tumor-specific mutational peptides whose expression could cover the maximum tumor regions for future immune therapies. We further demonstrated that combining tumor-specific peptides might enhance the efficacy of immunotherapy in both patient-derived cell (PDC) and patient-derived xenograft (PDX) models. PSERP efficiently retains precise spatial proteomic information within the tissue context and provides a deeper understanding of tissue biology and pathology at the molecular level.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"43 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145880","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":"BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial.","authors":"Hao Yao,Shi-Hui Ren,Lin-Hui Wang,Ming-Qiang Ren,Jiao Cai,Dan Chen,Ying He,Si-Han Lai,Bai-Tao Dou,Meng-Jiao Li,Yan-Ling Li,Ya-Li Cen,Alex H Chang,Yi Su,Ling Qiu,Fang-Yi Fan","doi":"10.1186/s13045-025-01713-2","DOIUrl":"https://doi.org/10.1186/s13045-025-01713-2","url":null,"abstract":"Relapsed/refractory multiple myeloma (RRMM) with extramedullary disease (EMD) represents a challenging condition, with limited treatment options and poor prognosis. We conducted a phase 1 clinical trial to evaluate the safety and effectiveness of a novel bispecific chimeric antigen receptor (CAR) T-cell therapy targeting two antigens, B-cell maturation antigen and G protein-coupled receptor class C group 5 member D (BCMA/GPRC5D), in this high-risk population. A total of 12 patients were enrolled, of whom 3 were excluded due to disease progression or death before CAR T-cell infusion, despite meeting the inclusion criteria, leaving 9 for analysis. The median follow-up was 6.08 months (Interquartile Range [IQR]: 0.9-16.5). All patients received BCMA/GPRC5D bispecific CAR T-cell therapy after bridging therapy with localized radiotherapy or Elranatamab. Efficacy assessments revealed that 100% of patients achieved partial response (PR) or better, with 44.4% achieving complete response (CR). Common adverse events included hematological toxicities such as anemia, leukopenia, and thrombocytopenia. Cytokine release syndrome (CRS) occurred in 66.7% of patients, all of which were grade 1-2, and no neurotoxicity (ICANS) was observed. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 60% and 63%, respectively. Median OS and PFS were not reached. Collectively, these findings highlight a potential therapeutic strategy involving BCMA/GPRC5D dual-targeted CAR T-cell therapy for patients with aggressive forms of multiple myeloma, particularly those with extramedullary disease, and support the need for further exploration and validation in larger, multi-center clinical studies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"8 1","pages":"56"},"PeriodicalIF":28.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087494","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":"Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies","authors":"Yunqing Lin, Ziyun Xiao, Fangxiao Hu, Xiujuan Zheng, Chenyuan Zhang, Yao Wang, Yanhong Liu, Dehao Huang, Zhiqian Wang, Chengxiang Xia, Qitong Weng, Leqiang Zhang, Yaoqin Zhao, Hanmeng Qi, Yiyuan Shen, Yi Chen, Fan Zhang, Jiaxin Wu, Pengcheng Liu, Jiacheng Xu, Lijuan Liu, Yanping Zhu, Jingliao Zhang, Wenbin Qian, Aibin Liang, Xiaofan Zhu, Tongjie Wang, Mengyun Zhang, Jinyong Wang","doi":"10.1186/s13045-025-01712-3","DOIUrl":"https://doi.org/10.1186/s13045-025-01712-3","url":null,"abstract":"T-cell malignancies are highly aggressive hematological tumors with limited effective treatment options. CAR-NK cell therapy targeting CD7 has emerged as a promising approach for treating T-cell malignancies. However, conventional CAR-NK cell therapy faces the challenges of cell fratricide due to CD7 expression on both malignant cells and normal NK cells. Additionally, engineering CARs into human tissue-derived NK cells demonstrates heterogeneity, low transduction efficiency, and high manufacturing costs. The human pluripotent stem cells (hPSCs) were genetically modified by knocking out the CD7 gene and introducing the CD7 CAR expression cassette to generate CD7 KO-CD7 CAR-hPSCs. These modified hPSCs were subsequently differentiated into CD7 KO-CD7 CAR-iNK cells using an efficient organoid induction method. The cytotoxicity of CD7 KO-CD7 CAR-iNK cells against CD7+ tumor cells was evaluated. Furthermore, we overexpressed the CXCR4 gene in CD7 KO-CD7 CAR-hPSCs and derived CXCR4-expressing CD7 KO-CD7 CAR-iNK (CRO-CD7 CAR-iNK) cells. The dynamics of CRO-CD7 CAR-iNK cells in vivo were tracked, and their therapeutic efficacy was assessed using human T-cell acute lymphoblastic leukemia (T-ALL) xenograft models. The CD7 KO-CD7 CAR-iNK cells derived from CD7 KO-CD7 CAR-hPSCs effectively avoided fratricide, demonstrated normal expansion, and exhibited potent and specific anti-tumor activity against CD7+ T-cell tumor cell lines and primary T-ALL cells. CXCR4 overexpression in CRO-CD7 CAR-iNK cells improved their homing capacity and extended their persistence in vivo. The CRO-CD7 CAR-iNK cells significantly suppressed tumor growth and prolonged the survival of T-ALL tumor-bearing mice. Our study provides a reliable strategy for the large-scale generation of fratricide-resistant CD7 CAR-iNK cells with robust anti-tumor effects from hPSCs, offering a promising cell product to treat T-cell malignancies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"230 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097333","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}