Experimental Hematology & Oncology最新文献

{"title":"Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.","authors":"Xinyu Li, Haiying Zhao","doi":"10.1186/s40164-025-00603-0","DOIUrl":"10.1186/s40164-025-00603-0","url":null,"abstract":"<p><p>Secretory autophagy is a classical form of unconventional secretion that integrates autophagy with the secretory process, relying on highly conserved autophagy-related molecules and playing a critical role in tumor progression and treatment resistance. Traditional autophagy is responsible for degrading intracellular substances by fusing autophagosomes with lysosomes. However, secretory autophagy uses autophagy signaling to mediate the secretion of specific substances and regulate the tumor microenvironment (TME). Cytoplasmic substances are preferentially secreted rather than directed toward lysosomal degradation, involving various selective mechanisms. Moreover, substances released by secretory autophagy convey biological signals to the TME, inducing immune dysregulation and contributing to drug resistance. Therefore, elucidating the mechanisms underlying secretory autophagy is essential for improving clinical treatments. This review systematically summarizes current knowledge of secretory autophagy, from initiation to secretion, considering inter-tumor heterogeneity, explores its role across different tumor types. Furthermore, it proposes future research directions and highlights unresolved clinical challenges.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"12"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074298","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":"Applications of liposomes and lipid nanoparticles in cancer therapy: current advances and prospects.","authors":"Zhe Cheng, Huichao Huang, Meilong Yin, Huaizheng Liu","doi":"10.1186/s40164-025-00602-1","DOIUrl":"10.1186/s40164-025-00602-1","url":null,"abstract":"<p><p>Liposomes and lipid nanoparticles are common lipid-based drug delivery systems and play important roles in cancer treatment and vaccine manufacture. Although significant progress has been made with these lipid-based nanocarriers in recent years, efficient clinical translation of active targeted liposomal nanocarriers remains extremely challenging. In this review, we focus on targeted liposomes, stimuli-responsive strategy and combined therapy in cancer treatment. We also summarize advances of liposome and lipid nanoparticle applications in nucleic acid delivery and tumor vaccination. In addition, we discuss limitations and challenges in the clinical translation of these lipid nanomaterials and make recommendations for the future research in cancer therapy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"11"},"PeriodicalIF":9.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074293","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":"A non-conditioned bone marrow transplantation mouse model to study clonal hematopoiesis and myeloid malignancies.","authors":"Sofia Bentivegna, Marwa Almosailleakh, Lin-Pierre Zhao, Mikkel Bruhn Schuster, Sébastien Benquet, Alexander Balhuizen, Helga Fibiger Munch-Petersen, Lene Dissing Sjö, Mads Hald Andersen, Nicolas Dulphy, Bo Porse, Kirsten Grønbæk","doi":"10.1186/s40164-025-00598-8","DOIUrl":"10.1186/s40164-025-00598-8","url":null,"abstract":"<p><p>Clonal hematopoiesis of indeterminate potential (CHIP) is a condition where blood or bone marrow cells carry mutations associated with hematological malignancies. Individuals with CHIP have an increased risk of developing hematological malignancies, atherosclerotic cardiovascular disease, and all-cause mortality. Bone marrow transplantation (BMT) of cells carrying CHIP mutations into irradiated mice are useful procedures to investigate the dynamics of clonal expansion and potential therapeutic strategies, but myeloablative conditioning can induce confounding effects. We established a non-conditioned BMT model using C57BL/6J-Kit^W-41J/J (W⁴¹) recipient mice to overcome the unwanted effects of irradiation. Conditional Tet2 deletion using tamoxifen was used to obtain Tet2^-/- cells from donor mice. Total BM Tet2^-/- cells were transplanted into W⁴¹ recipients, and longitudinal and terminal analyses at 10 months post-BMT were performed. We showed that W⁴¹ mice can be used for BMT procedures without myeloablative pre-conditioning. The transplantation of Tet2^-/- BM cells led to a progressive expansion of the donor cells in W⁴¹ recipients. By modulating the numbers of Tet2^-/- cells transplanted, recipient mice developed features of clonal hematopoiesis or myeloid malignancies. In conclusion, our model is an alternative to conventional irradiation-based transplantation models to study mechanisms underlying malignant hematopoiesis without confounding effects derived from pre-conditioning regimen.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"10"},"PeriodicalIF":9.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064722","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":"EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes.","authors":"Qi Zhang, Yingwan Luo, Li Ye, Yuxia Wang, Lu Wang, Wenli Yang, Wei Lang, Shuanghong Zhu, Lingxu Jiang, Weimei Jin, Chen Mei, Xinping Zhou, Yanling Ren, Liya Ma, Gaixiang Xu, Bowatte Gedara Lakmal Vimukthi Bandara Bowattage, Hongyan Tong, Jie Sun","doi":"10.1186/s40164-025-00600-3","DOIUrl":"10.1186/s40164-025-00600-3","url":null,"abstract":"<p><p>Myelodysplastic Syndromes (MDS) represent a group of heterogeneous myeloid clonal diseases derived from aberrant hematopoietic stem/progenitor cells. Enhancer of zeste homolog 2 (EZH2) is an important regulator in gene expression through methyltransferase-dependent or methyltransferase-independent mechanisms. Herein, we found EZH2 inhibition led to MDS cell pyroptosis through RNA Helicase A (RHA) down-regulation induced overexpression of S100A9, a key regulator of inflammasome activation and pyroptosis. Moreover, EZH2 inhibitor reduced tumor burden and prolonged the survival of the mice transplanted with MDS cells. In summary, our results uncovered a novel pyroptosis pathway induced by EZH2 inhibition and provided a rationale for EZH2 inhibitor treatment in MDS.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"9"},"PeriodicalIF":9.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064724","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":"Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.","authors":"Songting Shou, Ayidana Maolan, Di Zhang, Xiaochen Jiang, Fudong Liu, Yi Li, Xiyuan Zhang, En Geer, Zhenqing Pu, Baojin Hua, Qiujun Guo, Xing Zhang, Bo Pang","doi":"10.1186/s40164-025-00597-9","DOIUrl":"10.1186/s40164-025-00597-9","url":null,"abstract":"<p><p>Telomeres and telomerase play crucial roles in the initiation and progression of cancer. As biomarkers, they aid in distinguishing benign from malignant tissues. Despite the promising therapeutic potential of targeting telomeres and telomerase for therapy, translating this concept from the laboratory to the clinic remains challenging. Many candidate drugs remain in the experimental stage, with only a few advancing to clinical trials. This review explores the relationship between telomeres, telomerase, and cancer, synthesizing their roles as biomarkers and reviewing the outcomes of completed trials. We propose that changes in telomere length and telomerase activity can be used to stratify cancer stages. Furthermore, we suggest that differential expression of telomere and telomerase components at the subcellular level holds promise as a biomarker. From a therapeutic standpoint, combining telomerase-targeted therapies with drugs that mitigate the adverse effects of telomerase inhibition may offer a viable strategy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"8"},"PeriodicalIF":9.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052118","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":"Structural basis of FpGalNase and its combination with FpGalNAcDeAc for efficient A-to-O blood group conversion.","authors":"Meiling Zhou, Kaishan Luo, Chao Su, Yan Sun, Zuyan Huang, Shuo Ma, Xun Gao, Jiwei Wang, Chen Zhang, Pengcheng Han, Guoqiu Wu","doi":"10.1186/s40164-025-00599-7","DOIUrl":"10.1186/s40164-025-00599-7","url":null,"abstract":"<p><p>Transfusion safety and blood typing continue to present significant challenges in clinical practice, including risks of incorrect blood transfusions and blood shortages. One promising solution is the enzymatic conversion of all red blood cell (RBC) types into universal O-type RBCs. However, the major obstacle to this strategy is the relatively low catalytic efficiency of the enzymes involved. In this study, we investigated two enzymes from Flavonifractor plautii, N-acetylgalactosamine deacetylase (FpGalNAcDeAc) and galactosaminidase (FpGalNase), which demonstrate synergistic activity in efficiently converting A-type RBCs to O-type. We optimized treatment conditions, achieving over 99% conversion in just five minutes using phosphate buffer saline and a 16 nM enzyme concentration. Additionally, we engineered two fusion proteins, FpGalNAcDeAc-FpGalNase and FpGalNase-FpGalNAcDeAc, which showed a 28-fold increase in catalytic efficiency compared to the enzyme mixture. Using cryo-electron microscopy, we resolved the full-length structure of FpGalNase, identifying critical active site residues involved in its catalytic mechanism. This study provides essential structural and biochemical insights for clinical applications in blood group conversion, offering a promising approach for producing universal O-type RBCs.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"7"},"PeriodicalIF":9.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037732","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":"Construction and characterization of chimeric FcγR T cells for universal T cell therapy.","authors":"Juanjuan Zhao, Manling Chen, Xudong Li, Zhaoqi Chen, Wei Li, Rongqun Guo, Min Wang, Zhongxing Jiang, Yongping Song, Jianxiang Wang, Delong Liu","doi":"10.1186/s40164-025-00595-x","DOIUrl":"10.1186/s40164-025-00595-x","url":null,"abstract":"<p><strong>Background: </strong>Several approaches are being explored for engineering off-the-shelf chimeric antigen receptor (CAR) T cells. In this study, we engineered chimeric Fcγ receptor (FcγR) T cells and tested their potential as a versatile platform for universal T cell therapy.</p><p><strong>Methods: </strong>Chimeric FcγR (CFR) constructs were generated using three distinct forms of FcγR, namely CD16A, CD32A, and CD64. The functionality of CFR T cells was evaluated through degranulation assays, specific target lysis experiments, in vitro cytokine production analysis, and assessment of tumor xenograft destruction specificity in mouse models using different monoclonal antibodies (MoAbs).</p><p><strong>Results: </strong>Three types of CFR T cells were engineered, 16s3, 32-8a, 64-8a CFR T cells. In the presence of rituximab (RTX), cytotoxicity of all three types of CFR T cells against CD20⁺ Raji-wt, K562-CD20⁺, and primary tumor cells was significantly higher than that of the mock T cells (P < 0.001). When herceptin was used, all three types of CFR T cells exhibited significant cytotoxicity against HER2⁺ cell lines of SK-BR-3, SK-OV-3, and HCC1954 (P < 0.001). The cytotoxicity of 64-8a CFR T cells was significantly inhibited by free human IgG at a physiological dose (P < 0.001), which was not observed in 16s3, 32-8a CFR T cells. Compared to 32-8a CFR T cells, 16s3 CFR T cells exhibited more prolonged cytotoxicity than 32-8a CFR T cells (P < 0.01). In in vivo assays using xenograft models, 16s3 CFR T cells significantly prolonged the survival of mice xenografted with Raji-wt cells in the presence of RTX (P < 0.001), and effectively reduced tumor burden in mice xenografted with SK-OV-3 cells in the presence of herceptin (P < 0.05). No significant non-specific cytotoxicity of CFR T cells was found in vivo.</p><p><strong>Conclusion: </strong>The anti-tumor effects of the CFR T cells in vitro and in xenograft mouse models are mediated by specific MoAbs such as RTX and herceptin. The CFR T cells therefore have the features of universal T cells with specificity directed by MoAbs. 16s3 CFR T cells are chosen for clinical trials.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"6"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983248","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":"Combinatorial functionomics identifies HDAC6-dependent molecular vulnerability of radioresistant head and neck cancer.","authors":"Sharon Pei Yi Chan, Celestia Pei Xuan Yeo, Boon Hao Hong, Evelyn Mui Cheng Tan, Chaw Yee Beh, Eugenia Li Ling Yeo, Dennis Jun Jie Poon, Pek Lim Chu, Khee Chee Soo, Melvin Lee Kiang Chua, Edward Kai-Hua Chow","doi":"10.1186/s40164-024-00590-8","DOIUrl":"10.1186/s40164-024-00590-8","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is the primary treatment modality for most head and neck cancers (HNCs). Despite the addition of chemotherapy to radiotherapy to enhance its tumoricidal effects, almost a third of HNC patients suffer from locoregional relapses. Salvage therapy options for such recurrences are limited and often suboptimal, partly owing to divergent tumor and microenvironmental factors underpinning radioresistance. In this study, we utilized a combinatorial functionomics approach, the Quadratic Phenotypic Optimization Platform (QPOP), to rationally design drug pairings that exploit the molecular fingerprint and vulnerability of established in vitro isogenic radioresistant (RR)-HNC models.</p><p><strong>Methods: </strong>A QPOP-specific protocol was applied to RR-HNC models to rank and compare all possible drug combinations from a 12-drug set comprising standard chemotherapy, small molecule inhibitors and targeted therapies specific to HNC. Drug combination efficacy was evaluated by computing combination index scores, and by measuring apoptotic response. Drug targeting was validated by western blot analyses, and the Comet assay was used to quantify DNA damage. Enhanced histone deacetylase inhibitor (HDACi) efficacy in RR models was further examined by in vivo studies, and genetic and chemical inhibition of major Class I/II HDACs. Regulatory roles of HDAC6/SP1 axis were investigated using immunoprecipitation, gel shift and ChIP-qPCR assays. Comparative transcriptomic analyses were employed to determine the prognostic significance of targeting HDAC6.</p><p><strong>Results: </strong>We report the therapeutic potential of combining panobinostat (pan-HDAC inhibitor) with AZD7762 (CHK1/2 inhibitor; AstraZeneca) or ionizing radiation (IR) to re-sensitize RR-HNC cells and showed increased DNA damage underlying enhanced synergy. We further refined this RR-specific drug combination and prioritized HDAC6 as a targetable dependency in reversing radioresistance. We provide mechanistic insights into HDAC6-mediated regulation via a crosstalk involving SP1 and oncogenic and repair genes. From two independent patient cohorts, we identified a four-gene signature that may have discriminative ability to predict for radioresistance and amenable to HDAC6 inhibition.</p><p><strong>Conclusion: </strong>We have uncovered HDAC6 as a promising molecular vulnerability that should be explored to treat RR-HNC.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"5"},"PeriodicalIF":9.4,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970317","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":"Biomechanics in the tumor microenvironment: from biological functions to potential clinical applications.","authors":"Hao Peng, Zheng Chao, Zefeng Wang, Xiaodong Hao, Zirui Xi, Sheng Ma, Xiangdong Guo, Junbiao Zhang, Qiang Zhou, Guanyu Qu, Yuan Gao, Jing Luo, Zhihua Wang, Jing Wang, Le Li","doi":"10.1186/s40164-024-00591-7","DOIUrl":"10.1186/s40164-024-00591-7","url":null,"abstract":"<p><p>Immune checkpoint therapies have spearheaded drug innovation over the last decade, propelling cancer treatments toward a new era of precision therapies. Nonetheless, the challenges of low response rates and prevalent drug resistance underscore the imperative for a deeper understanding of the tumor microenvironment (TME) and the pursuit of novel targets. Recent findings have revealed the profound impacts of biomechanical forces within the tumor microenvironment on immune surveillance and tumor progression in both murine models and clinical settings. Furthermore, the pharmacological or genetic manipulation of mechanical checkpoints, such as PIEZO1, DDR1, YAP/TAZ, and TRPV4, has shown remarkable potential in immune activation and eradication of tumors. In this review, we delved into the underlying biomechanical mechanisms and the resulting intricate biological meaning in the TME, focusing mainly on the extracellular matrix, the stiffness of cancer cells, and immune synapses. We also summarized the methodologies employed for biomechanical research and the potential clinical translation derived from current evidence. This comprehensive review of biomechanics will enhance the understanding of the functional role of biomechanical forces and provide basic knowledge for the discovery of novel therapeutic targets.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"4"},"PeriodicalIF":9.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970316","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":"A cohort-based multi-omics identifies nuclear translocation of eIF5B /PD-L1/CD44 complex as the target to overcome Osimertinib resistance of ARID1A-deficient lung adenocarcinoma.","authors":"Dantong Sun, Helei Hou, Feiyue Feng, Weizheng Wu, Jingyu Tan, Tongji Xie, Jiayu Liu, Jinsong Wang, Haili Qian, Junling Li, Puyuan Xing","doi":"10.1186/s40164-024-00594-4","DOIUrl":"https://doi.org/10.1186/s40164-024-00594-4","url":null,"abstract":"<p><strong>Background: </strong>Osimertinib has emerged as a critical element in the treatment landscape following recent clinical trials. Further investigation into the mechanisms driving resistance to Osimertinib is necessary to address the restricted treatment options and survival advantages that are compromised by resistance in patients with EGFR-mutated lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>Spatial transcriptomic and proteomic analyses were utilized to investigate the mechanisms of Osimertinib resistance. Co-IP, MS, RNA-seq, ChIP-seq, RIP-seq, and ATAC-seq were performed in cell lines to further explore the mechanism. To validate the findings, in vitro and in vivo molecular experiments were conducted.</p><p><strong>Results: </strong>We found that the ARID1A deficiency results in resistance to Osimertinib by hindering programmed cell death through the EZH2/PTEN/E2F1 axis. This altered axis influences PD-L1 transcription through E2F1-mediated promoter activation and PD-L1 translation via the MDM2/eIF5B/PD-L1 axis. Subsequently, ARID1A deficiency results in increased expression of eIF5B and Importin-β1, promoting PD-L1 nuclear-translocation. The nuclear PD-L1 (nPD-L1) interacts with CD44, leading to nPD-L1 complex formation, activation of the RASGEF1A promoter, initiation of the Ras pathway, and contributing to Osimertinib resistance. Targeting the transcription, translation and nuclear-translocation of PD-L1 using lipid nanoparticles (LNPs) overcomes ARID1A deficiency-induced resistance.</p><p><strong>Conclusion: </strong>ARID1A deficiency promotes PD-L1 nuclear translocation and induces Osimertinib resistance.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"3"},"PeriodicalIF":9.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947144","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}