Experimental Hematology & Oncology最新文献

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Targeting collagen to optimize cancer immunotherapy. 靶向胶原蛋白优化癌症免疫治疗。
IF 13.5 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-29 DOI: 10.1186/s40164-025-00691-y
Yida Wang, Feng Zhang, Zhiwen Qian, Ying Jiang, Danping Wu, Lu Liu, Xin Ning, Jie Mei, Daozhen Chen, Yan Zhang
{"title":"Targeting collagen to optimize cancer immunotherapy.","authors":"Yida Wang, Feng Zhang, Zhiwen Qian, Ying Jiang, Danping Wu, Lu Liu, Xin Ning, Jie Mei, Daozhen Chen, Yan Zhang","doi":"10.1186/s40164-025-00691-y","DOIUrl":"10.1186/s40164-025-00691-y","url":null,"abstract":"<p><p>Collagen in the tumor microenvironment plays diverse biological roles, from serving as the structural framework of tumors to influencing immune responses, angiogenesis, and tumor progression. Consequently, developing strategies to optimize the suppression of collagen's promotive effects on tumor growth while maintaining its inhibitory functions on tumor initiation has become a key focus of cancer research and therapy. A significant challenge remains in identifying a biomarker with both high sensitivity and specificity for cancer diagnosis. This review, therefore, highlights the substantial value and clinical relevance of collagen as a biomarker throughout cancer onset and progression. It explores the fundamental link between collagen and immunotherapeutic outcomes, further illustrating how targeting collagen-along with its interactions with tumors and immune cells-can offer more reliable predictive markers for personalized immunotherapy. This approach ultimately enables the development of more tailored and standardized treatment regimens for patients with cancer.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"101"},"PeriodicalIF":13.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728974","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}
引用次数: 0
Targeted degradation of sICOSL reverses cytotoxic T cells dysfunction. 靶向降解sICOSL可逆转细胞毒性T细胞功能障碍。
IF 13.5 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-24 DOI: 10.1186/s40164-025-00692-x
Zhenghao Wu, Peng Zheng, Ruobing Qi, Yunxiao Xiao, Zihan Xi, Lei Dai, Tao Chen, Qianheng Wang, Furong Zhang, Rong Wang, Zimei Tang, Xiangwang Zhao, Jie Tan, Jie Ming, Ping Lei, Chunping Liu, Tao Huang
{"title":"Targeted degradation of sICOSL reverses cytotoxic T cells dysfunction.","authors":"Zhenghao Wu, Peng Zheng, Ruobing Qi, Yunxiao Xiao, Zihan Xi, Lei Dai, Tao Chen, Qianheng Wang, Furong Zhang, Rong Wang, Zimei Tang, Xiangwang Zhao, Jie Tan, Jie Ming, Ping Lei, Chunping Liu, Tao Huang","doi":"10.1186/s40164-025-00692-x","DOIUrl":"10.1186/s40164-025-00692-x","url":null,"abstract":"<p><p>Dysfunction of cytotoxic T cells (CTL) remains a major cause of tumor immune evasion and is correlated with poor cancer survival. Here, we found that increased soluble form of ICOSL (sICOSL) induced CTL dysfunction and was associated with shorter survival of patients with breast cancer. sICOSL emerged as a formidable adversary to CTLs, by directly triggering ICOS internalization and subsequent degradation-a critical blow to the co-stimulatory machinery essential for CTL activation. Our research shows that dipeptidyl peptidase-4 (DPP4) mainly breaks down sICOSL. Notably, certain chemotherapeutic drugs activate the histone methyltransferase Enhancer of zeste homolog 2 (EZH2), which in turn suppresses DPP4 expression. To address this issue, we have developed nanobody-DPP4 fusion proteins that can specifically degrade sICOSL, achieving substrate selectivity and tumor targeting. Overall, This work unveils that sICOSL orchestrates CTL dysfunction, and establishs targeted degradation of sICOSL as a new strategy for immunotherapy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"100"},"PeriodicalIF":13.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706921","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}
引用次数: 0
Decoding the metabolic dialogue in the tumor microenvironment: from immune suppression to precision cancer therapies. 解码肿瘤微环境中的代谢对话:从免疫抑制到精确的癌症治疗。
IF 13.5 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-22 DOI: 10.1186/s40164-025-00689-6
Ruoli Wang, Jincheng Zhuang, Qi Zhang, Wantao Wu, Xinrui Yu, Hao Zhang, Zongyi Xie
{"title":"Decoding the metabolic dialogue in the tumor microenvironment: from immune suppression to precision cancer therapies.","authors":"Ruoli Wang, Jincheng Zhuang, Qi Zhang, Wantao Wu, Xinrui Yu, Hao Zhang, Zongyi Xie","doi":"10.1186/s40164-025-00689-6","DOIUrl":"10.1186/s40164-025-00689-6","url":null,"abstract":"<p><p>The tumor microenvironment (TME) represents a metabolic battleground where immune cells and cancer cells vie for essential nutrients, ultimately influencing antitumor immunity and treatment outcomes. Recent advancements have shed light on how the metabolic reprogramming of immune cells, including macrophages, T cells, and DCs, determines their functional polarization, survival, and interactions within the TME. Factors such as hypoxia, acidosis, and nutrient deprivation drive immune cells toward immunosuppressive phenotypes, while metabolic interactions between tumors and stromal cells further entrench therapeutic resistance. This review synthesizes new insights into the metabolic checkpoints that regulate immune cell behavior, focusing on processes like glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and amino acid dependencies. We emphasize how metabolic enzymes (e.g., IDO1, ACLY, CPT1A) and metabolites (e.g., lactate, kynurenine) facilitate immune evasion, and we propose strategies to reverse these pathways. Innovations such as single-cell metabolomics, spatial profiling, and AI-driven drug discovery are transforming our understanding of metabolic heterogeneity and its clinical implications. Furthermore, we discuss cutting-edge therapeutic approaches-from dual-targeting metabolic inhibitors to biomaterial-based delivery systems-that aim to reprogram immune cell metabolism and enhance the effectiveness of immunotherapy. Despite the promise in preclinical studies, challenges persist in translating these findings to clinical applications, including biomarker validation, metabolic plasticity, and interpatient variability. By connecting mechanistic discoveries with translational applications, this review highlights the potential of immunometabolic targeting to overcome resistance and redefine precision oncology.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"99"},"PeriodicalIF":13.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689624","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}
引用次数: 0
Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis. 肿瘤微环境中肿瘤相关间充质干细胞/基质细胞与癌变的关系。
IF 9.4 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-17 DOI: 10.1186/s40164-025-00688-7
Li Sun, Xiaoli Cao, Baocheng Zhou, Jingyu Mei, Xinlan Zhao, Yuanyuan Li, Yongliang Yao, Mei Wang
{"title":"Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis.","authors":"Li Sun, Xiaoli Cao, Baocheng Zhou, Jingyu Mei, Xinlan Zhao, Yuanyuan Li, Yongliang Yao, Mei Wang","doi":"10.1186/s40164-025-00688-7","DOIUrl":"10.1186/s40164-025-00688-7","url":null,"abstract":"<p><p>Mesenchymal stem/stromal cells (MSCs) possess significant potential in regenerative medicine, attributed to their inherent capacity for site-specific homing to inflammatory regions, diverse differentiation abilities, and immunomodulatory functions. Tumors represent a substantial threat to human health, and therapeutic options remain limited. The inherent ability of MSCs to migrate towards tumor sites has been extensively utilized in cancer therapies. However, MSCs have shown ambiguous effects on tumors and contribute to the tumor microenvironment by trans-differentiation into different stromal cell types. Tumor-associated MSCs (TA-MSCs), derived from various tumor tissues, have been identified for their role in promoting tumor progression by interacting with tumor cells and other stromal components. As integral components of the tumor stroma, TA-MSCs provide a novel perspective for elucidating the mechanisms underlying malignancy. This review enhances our comprehension of TA-MSCs in solid tumors by summarizing evidence on their existence, differences from normal MSCs, heterogeneity, and roles in tumor initiation and progression. Furthermore, this review underscores the potential clinical implications of TA-MSCs for tumor diagnosis, prognosis prediction, and therapy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"97"},"PeriodicalIF":9.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658811","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}
引用次数: 0
Global burden and trends of hematologic malignancies based on Global Cancer Observatory 2022 and Global Burden of Disease 2021. 基于全球癌症观察站2022和全球疾病负担2021的全球血液系统恶性肿瘤负担和趋势
IF 9.4 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-17 DOI: 10.1186/s40164-025-00684-x
Tao Pan, Jiyue Zhang, Xiaomin Wang, Yuqin Song
{"title":"Global burden and trends of hematologic malignancies based on Global Cancer Observatory 2022 and Global Burden of Disease 2021.","authors":"Tao Pan, Jiyue Zhang, Xiaomin Wang, Yuqin Song","doi":"10.1186/s40164-025-00684-x","DOIUrl":"10.1186/s40164-025-00684-x","url":null,"abstract":"<p><strong>Background: </strong>Hematologic malignancies are one of the most common types of cancer. This study aims to assess the global burden of hematologic malignancies and analyze the global epidemiological trends.</p><p><strong>Methods: </strong>Through the Global Burden of Disease Study 2021 (GBD 2021) and the Global Cancer Observatory (GLOBOCAN) 2022 project, we comprehensively evaluated the global prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) of seven major hematologic malignancies, as well as their respective age-standardized rates (ASR) per 100,000 population. Regions were classified using the Socio-demographic Index (SDI) to evaluate the correlation between disease burden and economic level. In addition, we analyzed disease-related risk factors and predicted future trends up to 2040.</p><p><strong>Results: </strong>From 1990 to 2021/2022, the number of global hematologic malignancy cases showed a continuously increasing trend, especially for non-Hodgkin lymphoma. However, the age-standardized death rates (ASDR) and age-standardized DALY rates (ASDALYR) of all types of hematologic malignancies tended to be stable or decline. For acute lymphoblastic leukemia, the number of death cases, ASDR, and ASDALYR decreased significantly. Nevertheless, the trends of hematologic malignancies varied by gender, age, and SDI. The burden of hematologic malignancies was generally higher in the elderly and male populations. Of course, acute lymphoblastic leukemia also imposed a huge burden on children, Hodgkin lymphoma also significantly burdened young people. Moreover, regions with a higher SDI had a higher incidence rate. Deaths related to smoking and high body mass index still played an important role in various regions, especially in regions with a higher SDI. It is predicted that the global age-standardized incidence rates (ASIR) and ASDALYR will show a slow downward trend by 2040.</p><p><strong>Conclusions: </strong>Hematologic malignancies have remained a major global public health issue, with significant demographic and regional differences. The results of this study will provide a basis for analyzing the trends of the global disease burden of specific hematologic malignancies and offer a reference for health policymakers.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"98"},"PeriodicalIF":9.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658810","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}
引用次数: 0
Advancing precision antibody-drug conjugate therapy: unique proteogenomic profiles of tumor subsets in non-small cell lung cancer. 推进精确抗体-药物结合治疗:非小细胞肺癌中肿瘤亚群的独特蛋白质基因组图谱。
IF 9.4 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-11 DOI: 10.1186/s40164-025-00685-w
Edwin Lin, Ying-Chun Lo, Vivek Subbiah, Rajat Thawani, Aakash Desai
{"title":"Advancing precision antibody-drug conjugate therapy: unique proteogenomic profiles of tumor subsets in non-small cell lung cancer.","authors":"Edwin Lin, Ying-Chun Lo, Vivek Subbiah, Rajat Thawani, Aakash Desai","doi":"10.1186/s40164-025-00685-w","DOIUrl":"10.1186/s40164-025-00685-w","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) represent a promising therapeutic strategy for non-small cell lung cancer (NSCLC), targeting tumor-specific antigens with precision. However, the molecular heterogeneity of NSCLC necessitates multiplex biomarker approaches to optimize ADC efficacy. This study utilized transcriptomics and proteomics to characterize NSCLC subtypes with distinct ADC target expression profiles. RNA-seq data from two independent cohorts (537 tumors, 59 controls; 338 tumors, 311 controls) identified clusters defined by overexpression of CEACAM5, MET, and TACSTD2, while normal lung tissue exhibited moderate TACSTD2 and FOLR1 expression. Chi-squared residual analysis revealed no significant associations with disease stage or driver mutations. Proteomic and transcriptomic data from 110 tumors and 101 controls demonstrated strong concordance. These findings highlight the potential of ADCs to target NSCLC subsets with distinct proteogenomic profiles, independent of disease stage or mutational status, underscoring their broad applicability in precision oncology.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"96"},"PeriodicalIF":9.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616908","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}
引用次数: 0
Reduced morbidity and mortality of cGVHD in patients who received treatment with mesenchymal stromal cells for steroid-resistant aGVHD: long-term follow-up of a randomized phase 3 trial. 在接受间充质间质细胞治疗的激素抵抗性aGVHD患者中,cGVHD的发病率和死亡率降低:一项随机3期试验的长期随访
IF 9.4 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-09 DOI: 10.1186/s40164-025-00687-8
Ke Zhao, Ren Lin, Zhiping Fan, Zhen Li, Xiaoyong Chen, Li Xuan, Fen Huang, Na Xu, Xiuli Wu, Shaohua Chen, Jing Sun, Xi Zhang, Jianyu Weng, Yonghua Li, Yuhua Li, Dongjun Lin, Danian Nie, Shunqing Wang, Xiaojun Xu, Xiaohui Zhang, Yangqiu Li, A P Xiang, Yu Wang, Qifa Liu
{"title":"Reduced morbidity and mortality of cGVHD in patients who received treatment with mesenchymal stromal cells for steroid-resistant aGVHD: long-term follow-up of a randomized phase 3 trial.","authors":"Ke Zhao, Ren Lin, Zhiping Fan, Zhen Li, Xiaoyong Chen, Li Xuan, Fen Huang, Na Xu, Xiuli Wu, Shaohua Chen, Jing Sun, Xi Zhang, Jianyu Weng, Yonghua Li, Yuhua Li, Dongjun Lin, Danian Nie, Shunqing Wang, Xiaojun Xu, Xiaohui Zhang, Yangqiu Li, A P Xiang, Yu Wang, Qifa Liu","doi":"10.1186/s40164-025-00687-8","DOIUrl":"10.1186/s40164-025-00687-8","url":null,"abstract":"<p><strong>Background: </strong>Our open-label, multicenter, randomized, phase 3 trial showed that the incidence and severity of chronic graft-versus-host disease (cGVHD) reduced in steroid-resistant acute graft-versus-host disease (aGVHD) patients who underwent mesenchymal stromal cells (MSCs) treatments, but survival benefit was not received. Here, we present a post-hoc analysis of the 5-year follow-up to explore long-term survival and its underlying mechanism.</p><p><strong>Methods: </strong>This long-term follow-up trial included steroid-resistant aGVHD patients, who were randomly assigned (1:1) to receive MSCs (MSC group) (1 × 10<sup>6</sup> cells/kg once weekly for 4 consecutive weeks, 8 doses at most) or without MSCs treatment (control group). For this updated analysis, the 5-year endpoints were cumulative incidence of cGVHD, overall survival, cGVHD-free, relapse-free survival (CRFS), and relapse. To explore the mechanism, We investigated the changes in T, B cells, and signal joint T cell receptor excision DNA circles (sjTRECs).</p><p><strong>Results: </strong>Between September 2014 and March 2019, 198 patients were randomly assigned to the MSC group (n = 99) or the control group (n = 99). Extended follow-up showed the lower 5-year cumulative incidence of cGVHD (42.0% [95%CI 32.2-51.5] vs. 67.1% [55.6-76.3]; hazard ratio [HR] 2.19, 95%CI 1.47-3.27; P < 0.001), improved 5-year overall survival (60.4% [50.8-70.0] vs. 41.7% [31.9-51.5]; 0.63, 0.42-0.94; P = 0.023), CRFS (33.9% [24.5-43.3] vs. 20.9% [12.9-28.9]; 0.67, 0.48-0.93; P = 0.017) and no increase on relapse (13.6% [7.6-21.3] vs. 16.0% [9.5-23.9]; 1.24, 0.60-2.56; P = 0.568) for patients in MSC group compared with the control group. Clinical improvement of MSCs was accompanied by significant increases in regulatory T cells, CD4 + CD45RA + CD31 + naïve T, CD19 + CD27 + IgD- memory B cells, and sjTRECs.</p><p><strong>Conclusions: </strong>With extended follow-up, MSCs reduced the morbidity of cGVHD in aGVHD patients and improved overall survival and CRFS. Mechanistically, MSCs reduced cGVHD by thymus pathway.</p><p><strong>Trial registration: </strong>clinicaltrials.gov identifier: NCT02241018. Registration date: 16 September 2014, https://clinicaltrials.gov/ct2/show/NCT02241018 .</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"95"},"PeriodicalIF":9.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599796","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}
引用次数: 0
Recent advances and challenges of cellular immunotherapies in lung cancer treatment. 细胞免疫疗法在肺癌治疗中的最新进展和挑战。
IF 9.4 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-07 DOI: 10.1186/s40164-025-00679-8
Chengfei Yang, Yue Liu, Ziqi Huang, Sijin Liu, Xi Zhang, Quanxing Liu, Jigang Dai
{"title":"Recent advances and challenges of cellular immunotherapies in lung cancer treatment.","authors":"Chengfei Yang, Yue Liu, Ziqi Huang, Sijin Liu, Xi Zhang, Quanxing Liu, Jigang Dai","doi":"10.1186/s40164-025-00679-8","DOIUrl":"10.1186/s40164-025-00679-8","url":null,"abstract":"<p><p>Lung cancer is a major malignant tumor with high morbidity and fatality rates. For many years, traditional treatments for lung cancer have struggled to achieve a favorable outlook and prognosis. It is crucial to identify and innovate novel clinical therapeutic strategies and techniques to prevent tumor progression and prolong the survival time of patients with lung cancer. Cellular immunotherapies have revolutionized the treatment of malignant tumors and have been gradually applied in clinical practice. CAR-T therapy is the best-known cellular therapy and has achieved remarkable clinical outcomes in patients with hematological malignancies, but its effect on patients with lung cancer and other solid tumors is not satisfactory, partly because of the heterogeneity and complexity of lung cancers and the sterile TMEs. To further improve the clinical effect, multiple approaches and strategies have been adopted, including discovering new tumor antigen targets, improving safety, enhancing cytotoxicity, and increasing durability. Moreover, other cell-based immunotherapies have also showed great potential for the treatment of lung cancer, including TCR-T cells, TILs, CIK cells, NK cells, macrophages, and dendritic cells, which enriched the number of treatment choices for patients with lung cancer. In summary, the present article summarizes and highlights recent advances and challenges in the use of cellular immunotherapies for the treatment of lung cancer, which might stimulate new ideas for the further development of cellular immunotherapies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"94"},"PeriodicalIF":9.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583494","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}
引用次数: 0
iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia. 经CD226工程修饰的ipsc衍生NK细胞可有效控制急性髓系白血病。
IF 9.4 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-07 DOI: 10.1186/s40164-025-00686-9
Runze Cai, Binyan Lu, Xiangyu Zhao, Shixin Zhou, Yang Li
{"title":"iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia.","authors":"Runze Cai, Binyan Lu, Xiangyu Zhao, Shixin Zhou, Yang Li","doi":"10.1186/s40164-025-00686-9","DOIUrl":"10.1186/s40164-025-00686-9","url":null,"abstract":"<p><p>CD226 plays a vital role in NK cell cytotoxicity, interacting with its ligands on tumor targets. Acute myeloid leukemia (AML) cells have developed mechanisms to escape NK cell cytotoxicity, including inducing downregulation of CD226 on NK cells. Induced pluripotent stem cell -derived NK (iPSC-NK) cells offer an important source of standardized off-the-shelf NK cell therapy to treat AML patients. In this study, we engineered iPSC-NK cells with CD226 to assess the ability of killing AML cells. iPSC-NK cells engineered with CD226 have a typical NK cell phenotype and demonstrate improved anti-AML activity and multiple cytokines releasing at low effector-to-target ratios. Transcriptomic analysis revealed upregulation of immune effector function pathways associated with cytotoxicity and immune activation in CD226-overexpression iPSC-NK cells. In an AML xenograft model, mice treated with CD226 overexpression iPSC-NK cells exhibited significantly reduced leukemia burden, prolonged survival, decreased systemic inflammation compared to those treated with Control iPSC-NK cells. Overall, our study provided evidence that iPSC derived-NK cells engineered with CD226 represent a promising candidate for off-the-shelf immunotherapy, particularly in AML and other CD226 ligand-expressing malignancies.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"93"},"PeriodicalIF":9.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583493","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}
引用次数: 0
Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy. 嵌合抗原受体工程细胞免疫治疗的当前挑战和新机遇。
IF 9.4 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-07-02 DOI: 10.1186/s40164-025-00683-y
Yong Liu, Yifei Duan, Zefan Du, Bo Lu, Su Liu, Lindi Li, Mengyao Tian, Liang Li, Ran Yao, Cheng Ouyang, Mo Yang, Chun Chen
{"title":"Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.","authors":"Yong Liu, Yifei Duan, Zefan Du, Bo Lu, Su Liu, Lindi Li, Mengyao Tian, Liang Li, Ran Yao, Cheng Ouyang, Mo Yang, Chun Chen","doi":"10.1186/s40164-025-00683-y","DOIUrl":"10.1186/s40164-025-00683-y","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) engineered cellular immunotherapy offers the potential for precise targeting and elimination of tumor cells, providing a tailored approach to cancer treatment. CAR-T cells demonstrate significant anti-tumor activity among these therapies. Nonetheless, these therapies may trigger adverse effects, including inflammatory and neurotoxic reactions during treatment. Recent efforts have been directed toward enhancing efficacy by optimizing CAR design or modulating its activity. Compared to CAR-T cells, CAR-engineered natural killer cells (CAR-NK) present notable advantages, including various sources and diminished toxicity, and are gaining recognition in clinical research. CAR-macrophages (CAR-M), while sharing antigenic domains similar to those of CAR-T cells, display superior capabilities in antigen presentation and tumor penetration. As a result, there is significant enthusiasm surrounding investigations into CAR-NK and CAR-M cell immunotherapies. This review explores the existing environment and obstacles associated with immunotherapies that utilize CAR-T, CAR-NK, and CAR-M cells to inspire novel pathways for forthcoming clinical applications.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"92"},"PeriodicalIF":9.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552740","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}
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