Experimental Hematology & Oncology最新文献

{"title":"Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.","authors":"Valentina Morgera, Antonia Feola, Antonella Romano, Maria Vittoria Napoli, Armando Gabrielli, Vittorio Enrico Avvedimento, Antonio Porcellini, Antonio Pezone","doi":"10.1186/s40164-026-00779-z","DOIUrl":"10.1186/s40164-026-00779-z","url":null,"abstract":"<p><p>DNA damage response (DDR) inhibitors have reshaped precision oncology by exploiting tumor-specific vulnerabilities in genome maintenance and replication stress control. The clinical success of poly(ADP-ribose) polymerase (PARP) inhibitors-particularly in homologous recombination-deficient cancers-has validated this strategy, establishing a paradigmatic model for DDR-targeted therapies; however, both intrinsic and acquired resistance remain pervasive and limit durable benefit. In this Review, we analyze resistance mechanisms with a framework centered on PARP inhibitor biology, while extending key principles to other DDR-targeting strategies. We propose a hierarchical model that distinguishes dominant resistance drivers-mechanisms that restore DNA repair capacity or bypass the inhibited node (e.g., homologous recombination reactivation or checkpoint rewiring)-from adaptive resistance mechanisms that increase replication stress tolerance without restoring repair function, including replication-fork protection, metabolic reprogramming, cellular plasticity, and microenvironmental support. We discuss how tumor heterogeneity and therapy-imposed selective pressures shape clonal evolution and complicate biomarker development. We also critically evaluate combination strategies, highlighting why strong mechanistic rationale often fails to translate into consistent clinical benefit due to toxicity, scheduling constraints, and insufficient biomarker guidance. Finally, we outline priorities for moving beyond static genomic classifiers toward functional and longitudinal assessment of replication stress, DNA repair engagement, and tumor evolution to support more durable, biologically informed therapeutic strategies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of protein kinase CK2 remodels the tumor immune microenvironment and sensitizes lung cancer to PD-L1 blockade.","authors":"Sijia Zhang, Lihua Luo, Yangang Qu, Yan Zong, Leichong Chen, Qianwen Li, Zhenyu Li, Jian Wang, Xiaohua Jie, Yun Xia, Bin Qu, Junyu Li, Chunwei Xu, Bingwen Zou, Hongqing Zhuang, Rui Meng","doi":"10.1186/s40164-026-00778-0","DOIUrl":"10.1186/s40164-026-00778-0","url":null,"abstract":"<p><strong>Background: </strong>Protein kinase CK2 is a pleiotropic oncogenic serine/threonine kinase implicated in multiple cancer-associated signaling pathways. However, its role in shaping the tumor immune microenvironment (TIME) and regulating immune checkpoint stability remains incompletely understood.</p><p><strong>Methods: </strong>We integrated analyses of two independent lung cancer patient cohorts with mechanistic and therapeutic studies in lung cancer models. CK2α expression was evaluated in relation to immune infiltration, clinical outcome, and response to immune checkpoint blockade (ICB). The therapeutic impact of combining PD-L1 mAb treatment with three structurally distinct CK2 inhibitors (TBB, CX4945, and SGC-CK2-1) was assessed in vivo. Underlying mechanisms were investigated using transcriptomic profiling, immunophenotyping, and biochemical analyses.</p><p><strong>Results: </strong>Elevated CK2α expression was clinically associated with an immunosuppressive tumor microenvironment (TME), reduced CD8⁺ T cell infiltration, inferior survival, and diminished responsiveness to ICB. In preclinical models, pharmacological CK2 inhibition suppressed tumor growth and reprogrammed the TIME by enhancing T cell infiltration, activation, and proliferation, while alleviating CD8⁺ T cell exhaustion. Importantly, CK2 inhibition sensitized lung tumors to PD-L1 blockade, resulting in robust antitumor efficacy, including complete tumor regression and durable immune protection in a subset of treated mice. Mechanistically, CK2 inhibition reduced PD-L1 protein stability through a defined CK2-TRAF6-PD-L1 axis, in which TRAF6 acts as a critical E3 ubiquitin ligase mediating site-specific ubiquitination of PD-L1 at lysine 281, thereby promoting its proteasomal degradation.</p><p><strong>Conclusions: </strong>These findings identify CK2 as a key regulator of tumor immune evasion and uncover a previously unrecognized post-translational checkpoint controlling PD-L1 stability via TRAF6-dependent ubiquitination. Targeting CK2 represents a rational strategy to sensitize immunologically \"cold\" tumors to ICBs and enhance immunotherapeutic efficacy in lung cancer.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13231707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISX-TWIST1 reprograms CD47-inflammasome signaling to reshape the immune microenvironment in liver cancer.","authors":"Li-Ting Wang, Ming-Hong Lin, Yi-Chuan Li, Shen-Nien Wang, Chee-Yin Chai, Jung-Mao Hsu, Shyh-Shin Chiou, Hsin-Ying Clair Chiou, Shau-Ku Huang, Mien-Chie Hung, Shih-Hsien Hsu","doi":"10.1186/s40164-026-00777-1","DOIUrl":"10.1186/s40164-026-00777-1","url":null,"abstract":"<p><p>Immunotherapies have shown promise effectiveness in cancer treatment, yet the complex tumor microenvironment poses challenges to their efficacy. The interaction between immune checkpoints in malignant and immune cells is crucial for cancer cells to evade the host's immune response, but the impact of tumor cell immune checkpoint molecules on disease progression remains incompletely understood. Our study uncovers a significant link between the CD47 signals, inflammasomes and intestine-specific homeobox (ISX), correlating strongly with lesion count, disease stage, and lymph vascular invasion. Elevated CD47 expression activates CD47-SIRPα signaling to promote M2-like macrophage polarization, accompanied by inflammasome activation and cytokine production within the tumor microenvironment and memory T cell differentiation within the hepatic microenvironment, intensifying disease progression. In xenograft and chronic hepatic tumor model featuring a liver-specific ISX mutant, the elimination of M2-like TAM macrophages and TRM cells halts disease advancement. Through transcriptomic analysis and molecular evidence, we unveil the interaction of ISX with TWIST1, triggering CD47-SIRPα and inflammasome activation by binding to specific degenerate sequences (\"-GGDWYR-\") in the promoter regions of CD47-SIRPα signals and inflammasome-related genes. These findings underscore the pivotal role of the ISX-CD47 axis in liver disease and tumor progression. They offer promising insights into potential treatments for liver disease, shedding light on new therapeutic strategies with the potential to improve patient outcomes.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining circulating tumor cell and circulating cell-free DNA analyses broadens clinical applicability of liquid biopsy in high grade serous tubo-ovarian carcinoma.","authors":"Beatrice Cavina, Simona Corrà, Camelia Alexandra Coadă, Monica De Luise, Silvia Lemma, Sara Coluccelli, Antonio De Leo, Stella Di Costanzo, Francesco Mezzapesa, Giulia Girolimetti, Pierandrea De Iaco, Anna Maria Porcelli, Anna Myriam Perrone, Dario de Biase, Giuseppe Gasparre, Ivana Kurelac","doi":"10.1186/s40164-026-00774-4","DOIUrl":"10.1186/s40164-026-00774-4","url":null,"abstract":"<p><p>Liquid biopsy is a promising strategy for detecting and monitoring neoplastic diseases, with circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) being the most common objects of investigation. Studies are mainly focusing on these biomarkers separately, and simultaneous detection has never been attempted in high grade serous tubo-ovarian carcinoma (HGSOC). Here, we assess whether tandem CTC/ctDNA analysis improves the efficiency of detecting HGSOC via peripheral blood liquid biopsy. For CTC identification, gene expression assays and TP53 next-generation sequencing (NGS) were tested using healthy donor samples spiked with known cancer cell numbers. Both approaches detected as few as five spiked cancer cells, showing high analytical sensitivity and specificity. Validation in HGSOC patients and healthy controls revealed better performance of TP53 NGS, as it correctly identified the disease in 47% liquid biopsies, compared to 13% sensitivity obtained by gene expression assay. TP53 NGS was also applied for ctDNA detection, where analytical validity was ensured by calculating 0.31% as the optimal variant allele frequency threshold for mutation calling. Clinical validation demonstrated that ctDNA approach, with sensitivity of 70%, outperformed CTC-based methods. Combining ctDNA/CTC analysis improved disease detection rate in two HGSOC cohorts, achieving, respectively, 73.3% and 93.3% sensitivity, which would translate to an absolute gain of additional 13 patients per 100 cases being detected if combined approach is applied compared to ctDNA method alone. Interestingly, we found private CTC variants, and shared ctDNA/CTC mutations undetected in solid biopsy, highlighting the ability of dual-analyte approach to capture tumor heterogeneity and allow mutation cross-validation, which is particularly useful in contexts when solid biopsy is not available. Our study reveals the complementary value of simultaneous ctDNA/CTC analysis in HGSOC, advancing the translational potential of liquid biopsy integration for management of this disease, especially regarding early detection, chemotherapy response evaluation and relapse detection.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.","authors":"Yu-Shun Wang, Li-Heng Qian, Cui-Cui Liu, Ke-Da Yu","doi":"10.1186/s40164-026-00775-3","DOIUrl":"10.1186/s40164-026-00775-3","url":null,"abstract":"<p><p>Metabolic reprogramming and genome instability represent two fundamental hallmarks of cancer. Emerging studies now demonstrate that specific metabolic alterations directly fuel replication stress, DNA damage, and compromised DNA damage response. This underscores that metabolites are not merely passive by-products but active biochemical regulators of genome instability. Perturbation of specific metabolic pathways can preferentially unmask these vulnerabilities for therapeutic targeting. In this review, we propose an integrated framework highlighting metabolism-induced genome instability as a potential therapeutic target. By delineating the metabolic targets that induce genome instability, we provide a comprehensive overview of the complex interplay between metabolic pathways and genome stability. We further highlight that metabolism-induced genome instability can be strategically exploited to potentiate standard-of-care therapies. Collectively, these insights redefine metabolism-induced genome instability as a targetable vulnerability of cancer. This systematic synthesis provides a mechanistic rationale for next-generation therapeutic designs in which metabolic interventions are leveraged to convert genome instability into actionable clinical vulnerabilities.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.","authors":"Lizhou Song, Yue Shu, Tian Zhou, Yi Wang, Haoling Zhang, Yan Liao, Chenglong Zhu, Wangzheqi Zhang, Zui Zou","doi":"10.1186/s40164-026-00773-5","DOIUrl":"10.1186/s40164-026-00773-5","url":null,"abstract":"<p><p>The resistance to treatment and the high chance of death associated with cancer still remain key problems that need breakthrough in biology and medicine. Ferroptosis is a newly discovered form of regulated cell death that is driven by iron and lipid peroxidation. Research reveals that ferroptosis plays an important role in tumour initiation, progression, and treatment. Furthermore, this process is mediated by distinct and dynamic molecular mechanisms. All of this information about the importance of ferroptosis will provide new targets and opportunities for cancer therapies. Cross-talk with other cell death pathways (e.g. apoptosis, necroptosis, autophagy) can modulate ferroptosis, and in some contexts these interactions may inhibit ferroptosis execution or activate adaptive survival responses in tumour cells. Ferroptosis has an initiation stage, a subsequent execution stage, and lastly a termination stage. Moreover, the sensitivity and response mechanisms of tumour cells to ferroptosis have significant differences in the early stage, progressive stage, metastatic stage, recurrent stage, etc. Due to the heterogeneous microenvironmental characteristics of hypoxic regions, immune-infiltrated regions and fibrotic regions in the spatial area of the tumour microenvironment (TME), these regions dynamically interact with ferroptosis. At present, strategies based on ferroptosis for tumour therapy have shown great promise. The use of advanced stimulus-responsive nanotechnology with classical ferroptosis inducers will enable the precise delivery and slow release of these inducers to enhance therapeutic efficacy and minimise damage to normal tissues. Nonetheless, several hurdles remain for clinical translation. A detailed examination of the complex regulatory networks in the TME, the development of scalable manufacturing processes for nanosystems, and the identification of non-invasive biomarkers to monitor the efficacy of ferroptosis are critical breakthrough points in the translation of ferroptosis-based therapy from bench to bedside.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Novel non-viral in vivo CAR-T therapies: latest updates from the 2025 ASH annual meeting.","authors":"Bin Xue, Yifan Liu, Aibin Liang, Wenjun Zhang","doi":"10.1186/s40164-026-00772-6","DOIUrl":"10.1186/s40164-026-00772-6","url":null,"abstract":"","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13054966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of patient-derived organoids reveals that E3 ligase COP1 promotes liver metastasis and oxaliplatin resistance in colorectal cancer through LUZP1 degradation and MYL9 phosphorylation.","authors":"Ruijia Zhang, Wenqin Luo, Qikai Zhou, Dongguo Liang, Yuankai Hao, Fan Chen, Yulin Qiu, Yixian Cao, Zezhi Shan, Yu Zhang, Qingguo Li, Sanjun Cai, Dakui Luo, Shaobo Mo, Bin Ma, Xinxiang Li","doi":"10.1186/s40164-026-00771-7","DOIUrl":"10.1186/s40164-026-00771-7","url":null,"abstract":"<p><p>Colorectal cancer liver metastasis (CRLM) and chemotherapy resistance remain major clinical challenges, with the underlying molecular mechanisms yet to be fully elucidated. In this study, based on analyses of five initial clinical cohorts from FUSCC, the E3 ubiquitin ligase COP1 was identified as a critical driver of CRLM and resistance to oxaliplatin-based chemotherapy. Using an organoid biobank derived from paired primary colorectal tumors and liver metastases, integrated multi-omics analyses (WES, bulk RNA-seq, scRNA-seq) of patient-derived organoids (PDOs) from CRLM revealed significantly elevated COP1 expression in liver metastases compared to primary tumors. High COP1 levels were associated with poor prognosis, increased liver metastatic burden, and resistance to oxaliplatin-based chemotherapy. In vitro and in vivo functional experiments demonstrated that COP1 facilitates CRLM progression by ubiquitinating and degrading LUZP1, thereby releasing DAPK3 from LUZP1-mediated suppression. This process leads to enhanced MYL9 phosphorylation and activation of epithelial-mesenchymal transition (EMT) as well as the JAK2-STAT3-CCND2 signaling axis-pathways crucial for liver metastasis and resistance to oxaliplatin-based chemotherapy. These findings establish the COP1-LUZP1-MYL9 axis as a therapeutic target for CRLM and oxaliplatin-based chemoresistance. Clinically, COP1 expression profiling in PDOs from postoperative specimens enables a precision strategy for managing oxaliplatin-based chemoresistance, especially in the context of FOLFOX.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic immune properties of carrier MSC impact on the clinical outcome of children with solid tumors receiving oncolytic virotherapy.","authors":"Alvaro Morales-Molina, Lidia Franco-Luzón, Patricia Garcia-Rodriguez, Africa González-Murillo, Javier García-Castro, Manuel Ramírez","doi":"10.1186/s40164-026-00768-2","DOIUrl":"10.1186/s40164-026-00768-2","url":null,"abstract":"<p><p>Our previous clinical data showed that autologous mesenchymal stromal cells (MSCs) can be used as carriers for the systemic delivery of oncolytic adenoviruses in children with advanced cancers, a therapy known as Celyvir. Despite achieving clinical remissions, treatment responses have been heterogeneous. Here, we sought to determine whether intrinsic biological characteristics of carrier MSCs influence therapeutic outcomes. Transcriptomic profiling was performed on MSCs from responder and non-responder patients to identify pathways differentially regulated according to clinical response. Expression of MAVS (mitochondrial antiviral signaling), NF-κB activation, and secretion of pro-inflammatory cytokines were analyzed in MSCs and Celyvir products both at baseline and after adenoviral infection. Among the pathways differentially regulated in MSCs according to treatment response, MAVS was identified as a relevant modulator, showing significantly lower expression in Celyvir products from responder patients. Consistently, MSCs and Celyvir products from responders exhibited reduced NF-κB activation and secreted significantly lower levels of pro-inflammatory cytokines at baseline and post-infection. To validate these findings, immunocompetent mice were treated with murine Celyvir prepared using MAVS-deficient (MAVS^-/-) MSCs as a model of \"silent cells\". Accordingly, murine Celyvir treatment using MAVS^-/- MSCs significantly enhanced antitumor efficacy compared to wild-type MSCs. Tumors from animals treated with murine Celyvir MAVS^-/- displayed increased infiltration of T cells and NK cells. In summary, carrier MSCs with a diminished antiviral innate immune response-characterized by low MAVS expression and attenuated pro-inflammatory signaling-provide a therapeutic advantage for systemic delivery of oncolytic viruses. These findings support the incorporation of \"silent\" MSCs, spontaneous or induced, into next-generation clinical trials aiming to optimize cell-based oncolytic virotherapy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13047822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and translational advances in regulatory T cell-based strategies in allogeneic hematopoietic stem cell transplantation: highlights from ASH 2025.","authors":"Somayeh Yazdanparast, Saeid Abroun, Tahereh Rostami, Saeed Mohammadi","doi":"10.1186/s40164-026-00769-1","DOIUrl":"10.1186/s40164-026-00769-1","url":null,"abstract":"<p><p>Regulatory T cells (T_regs), winners of the 2025 Nobel Prize in Physiology or Medicine, emerged as an unsung giant of peripheral immune tolerance after allogeneic hematopoietic stem cell transplantation (allo-HSCT). These cells exert influence across four interconnected immunological axes encompassing graft-versus-leukemia (GVL), graft-versus-host disease (GVHD), relapse, and viral infection. This correspondence highlights key advancements in T_reg-based interventions in allo-HSCT, ranging from basic research to clinical applications, as presented at the ASH 2025 Annual Meeting. Accordingly, T_regs are used as GVHD prophylaxis via the Orca-T platform and as a therapeutic strategy for steroid-refractory (SR)-GVHD patients. Experimental studies further pave the way to address existing limitations toward next-generation T_reg-based cell therapy in allo-HSCT.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13047817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}