Experimental Hematology & Oncology最新文献

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Elevated TIM3 expression on bone marrow T cells drives immune dysfunction in early relapsed blood cancer after allogeneic hematopoietic stem cell transplantation. 骨髓T细胞TIM3表达升高驱动异基因造血干细胞移植后早期复发血癌的免疫功能障碍。
IF 13.5 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-08-14 DOI: 10.1186/s40164-025-00697-6
Thi Thuy Duong Pham, Su-Young Choi, Jeong Suk Koh, Bu-Yeon Heo, Sang-Woo Lee, Myung-Won Lee, Wonhyoung Seo, Yunseon Jang, Jung-Hyun Park, Deog-Yeon Jo, Seungyeul Yoo, Jaeyul Kwon, Ik-Chan Song
{"title":"Elevated TIM3 expression on bone marrow T cells drives immune dysfunction in early relapsed blood cancer after allogeneic hematopoietic stem cell transplantation.","authors":"Thi Thuy Duong Pham, Su-Young Choi, Jeong Suk Koh, Bu-Yeon Heo, Sang-Woo Lee, Myung-Won Lee, Wonhyoung Seo, Yunseon Jang, Jung-Hyun Park, Deog-Yeon Jo, Seungyeul Yoo, Jaeyul Kwon, Ik-Chan Song","doi":"10.1186/s40164-025-00697-6","DOIUrl":"10.1186/s40164-025-00697-6","url":null,"abstract":"<p><p>Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading cause of treatment failure in patients with hematologic malignancies. To better understand the mechanisms underlying early relapse (ER), we comprehensively explored the expression of inhibitory receptors (IRs) in bone marrow (BM) T cells at differentiation stage and examined transcriptional differences. Among the evaluated IRs, TIM3 was significantly upregulated in CD3<sup>+</sup>T cells of patients with ER compared to patients with complete remission (CR). Notably, double-negative T (DNT) cells, a unique subset with MHC-independent cytotoxic potential, constituted a high proportion of BM T cells and expressed increased TIM3 expression in ER patients. Moreover, regulatory T cells (Tregs) showed elevated TIM3 levels, contributing to an immunosuppressive microenvironment after allo-HSCT. Transcriptomic analysis revealed downregulation of cytotoxic granules and effector genes in DNT cells from ER patients. Functional assays demonstrated that TIM3 blockade with sabatolimab restored T cell cytotoxicity, leading to enhanced leukemia cell apoptosis in ER patients. These findings highlight TIM3 as a critical regulator of T cell exhaustion and immune suppression in patients with ER and provide a rationale for the therapeutic use of TIM3 blockade in preventing and treating relapses after allo-HSCT.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"107"},"PeriodicalIF":13.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854981","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
In-depth insight into tumor-infiltrating stromal cells linked to tertiary lymphoid structures and their prospective function in cancer immunotherapy. 深入了解与三级淋巴结构相关的肿瘤浸润基质细胞及其在癌症免疫治疗中的预期功能。
IF 13.5 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-08-10 DOI: 10.1186/s40164-025-00695-8
Maedeh Radandish, Niloofar Mashhadi, Amir Hossein Aghayan, Motahareh Taghizadeh, Sara Salehianfard, Sheida Yahyazadeh, Omid Vakili, Somayeh Igder
{"title":"In-depth insight into tumor-infiltrating stromal cells linked to tertiary lymphoid structures and their prospective function in cancer immunotherapy.","authors":"Maedeh Radandish, Niloofar Mashhadi, Amir Hossein Aghayan, Motahareh Taghizadeh, Sara Salehianfard, Sheida Yahyazadeh, Omid Vakili, Somayeh Igder","doi":"10.1186/s40164-025-00695-8","DOIUrl":"10.1186/s40164-025-00695-8","url":null,"abstract":"<p><strong>Background and purpose: </strong>The tumor microenvironment (TME) is widely acknowledged as a pivotal regulator of cancer progression. However, the dualistic role of tertiary lymphoid structures (TLSs), which serve as critical immune hubs within the TME, remains incompletely characterized, particularly with respect to their context-dependent capacity to either inhibit or facilitate tumor development. This review aims to synthesize current understanding of the complex interactions between stromal cells and TLSs, addressing existing gaps in mechanistic insight and exploring therapeutic avenues to exploit TLS plasticity.</p><p><strong>Key reviewed topics: </strong>The current study critically reviews the mechanisms by which stromal components, including cancer-associated fibroblasts and endothelial cells, contribute to TLS neogenesis through chemokine-mediated recruitment of lymphocytes. Furthermore, it highlights the dual functional roles of TLSs as sites of both anti-tumor immune activation and immunosuppression, notably via the enrichment of regulatory T cells. The clinical implications of mature TLS presence, particularly their association with improved patient prognosis and enhanced therapeutic responsiveness, are also analyzed.</p><p><strong>Main conclusions: </strong>TLSs demonstrate a bifunctional nature, wherein their spatial organization and dynamic interactions with stromal elements dictate the balance between immune activation and tolerance within the TME. While mature TLSs are generally correlated with favorable clinical outcomes, their potential to foster immunosuppressive microenvironments necessitates the development of precision-targeted interventions. The interplay between stromal cells and TLSs represents a promising therapeutic axis for modulating the tumor immune milieu.</p><p><strong>Future perspectives: </strong>Future research should prioritize strategies aimed at promoting TLS maturation, disrupting immunosuppressive niches, and integrating TLS-modulating agents with existing immunotherapeutic regimens to enhance clinical efficacy. Additionally, the identification of robust biomarkers reflective of TLS functional states and the rigorous validation of stromal-targeted therapies within combinatorial treatment frameworks are imperative for advancing translational applications.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"105"},"PeriodicalIF":13.5,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816115","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
An ureido-substituted benzenesulfonamide carbonic anhydrase inhibitor exerts a potent antitumor effect in vitro and in vivo. 脲基取代苯磺酰胺碳酸酐酶抑制剂在体外和体内均具有较强的抗肿瘤作用。
IF 13.5 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-08-08 DOI: 10.1186/s40164-025-00690-z
Giorgia Gazzaroli, Camilla Tavani, Serena Filiberti, Maria Luisa Massardi, Marta Turati, Giulia Garattini, Thomas S Peat, Giuseppe Pieraccini, Andrea Angeli, Claudiu T Supuran, Fabrizio Carta, Arianna Giacomini, Roberto Ronca
{"title":"An ureido-substituted benzenesulfonamide carbonic anhydrase inhibitor exerts a potent antitumor effect in vitro and in vivo.","authors":"Giorgia Gazzaroli, Camilla Tavani, Serena Filiberti, Maria Luisa Massardi, Marta Turati, Giulia Garattini, Thomas S Peat, Giuseppe Pieraccini, Andrea Angeli, Claudiu T Supuran, Fabrizio Carta, Arianna Giacomini, Roberto Ronca","doi":"10.1186/s40164-025-00690-z","DOIUrl":"10.1186/s40164-025-00690-z","url":null,"abstract":"<p><p>Carbonic anhydrase IX (CA IX) is a tumor-specific metallo-enzyme upregulated during hypoxic conditions and implicated in several pathophysiological processes where tissue pH regulation is required such as cancer, cell invasion, metastatic and stem-like features, drug resistance and recurrence. Indeed, CA IX expression has been correlated with poor prognosis, aggressiveness and disease progression in several solid tumors, and its targeting has been proposed as a therapeutic approach to treat aggressive cancers. To date, several CA IX targeting approaches have been developed to inhibit its activity in neoplastic tissues including the clinical grade (Phase Ib/II) ureido-substituted benzenesulfonamide SLC-0111, which has been widely investigated over the past years. In this study, we carried out a detailed characterization of a SLC-0111 derivative, FC-531, evaluating its anti-tumor potential in parallel with SLC-0111 on a panel of human cell lines representative of different cancer types. Finally, we evaluated the safety profile of FC-531 in vivo and demonstrated its capacity to reduce tumor growth and metastatization in vivo. Together, our data provide the rationale for the exploitation of FC-531 as a potent CA IX inhibitor for the management of different CA IX- expressing solid tumors.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"104"},"PeriodicalIF":13.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803948","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
Incidence, mortality, and risk factors of bladder, kidney, prostate and testicular cancers in China and comparisons with the United States, the United Kingdom, Japan, and the Republic of Korea: an up-to-date overview based on the Global Burden of Disease 2021. 中国膀胱癌、肾癌、前列腺癌和睾丸癌的发病率、死亡率和危险因素,以及与美国、英国、日本和韩国的比较:基于2021年全球疾病负担的最新概述
IF 13.5 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-08-06 DOI: 10.1186/s40164-025-00694-9
Gaohaer Kadeerhan, Zhongji Jiang, Hong Guo, Xinzhi Ma, Jin Zhang, Wenmin Guo, Jiedong Jia, Yibo Gao, Dongwen Wang
{"title":"Incidence, mortality, and risk factors of bladder, kidney, prostate and testicular cancers in China and comparisons with the United States, the United Kingdom, Japan, and the Republic of Korea: an up-to-date overview based on the Global Burden of Disease 2021.","authors":"Gaohaer Kadeerhan, Zhongji Jiang, Hong Guo, Xinzhi Ma, Jin Zhang, Wenmin Guo, Jiedong Jia, Yibo Gao, Dongwen Wang","doi":"10.1186/s40164-025-00694-9","DOIUrl":"10.1186/s40164-025-00694-9","url":null,"abstract":"<p><strong>Background: </strong>The burden of genitourinary cancers has significantly changed in China over the recent decades. This study aims to identify the epidemiological trends and disparities in four common genitourinary cancers, including bladder, kidney, prostate, and testicular cancers, to inform public health strategies and interventions.</p><p><strong>Methods: </strong>Based on the Global Burden of Disease Study 2021, we examined incident cases, mortality, age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), mortality-to-incidence ratios (MIRs), and risk factors for four genitourinary cancers globally and in the East Asia and Pacific, China, Japan, the Republic of Korea, the United States, and the United Kingdom from 1990 to 2021 across four specified age groups: 0-14, 15-49, 50-74, and ≥ 75 years. Trend analysis was conducted using Joinpoint analysis to calculate the average annual percentage changes (AAPCs). Decomposition analysis was performed to identify the population-level factors contributing to these trends.</p><p><strong>Results: </strong>In 2021, China reported approximately 266,887 incident cases and 108,589 deaths from genitourinary cancers, exhibiting distinct age-related patterns. ASIRs for male kidney cancer among those aged 0-14 years and testicular cancer among those aged ≥ 75 years, as well as ASMRs for male bladder cancer aged 15-49 years and testicular cancer aged ≥ 75 years, were higher in China than in the studied regions and countries. The MIRs for genitourinary cancers were generally higher in China. From 1990 to 2021, a notable increase in ASIRs for genitourinary cancers in both sexes, as well as ASMRs for male kidney and prostate cancers, across age groups ranging from 15 to 49 years to ≥ 75 years was observed in China, accompanied by higher AAPCs. The decomposition analysis identified the key population-level contributors to the incidence and mortality trends of genitourinary cancers, highlighting the varying influences of aging, population growth, and epidemiological changes. Smoking-related genitourinary cancer deaths remained high in Chinese males, and mortality related to high body mass index for kidney cancer and elevated fasting plasma glucose levels for bladder cancer also increased.</p><p><strong>Conclusions: </strong>The distinct age-specific patterns, elevated rates within specific age groups, and marked upward temporal trends of genitourinary cancers in China underscore the critical need for targeted, age-stratified public health interventions.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"103"},"PeriodicalIF":13.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793875","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
Bisecting GlcNAc enhances CD8+ T cell-mediated killing of breast cancer by suppressing PD-L1 expression and its binding to PD-1. 分割GlcNAc可通过抑制PD-L1的表达及其与PD-1的结合来增强CD8+ T细胞介导的乳腺癌杀伤。
IF 13.5 1区 医学
Experimental Hematology & Oncology Pub Date : 2025-08-04 DOI: 10.1186/s40164-025-00693-w
Xueting Ren, Jinpeng Wu, Jing Li, Zhen Zhai, Xiang Li, Feng Guan, Meng Wang, Xiaobin Ma, Zengqi Tan, Huafeng Kang, Shuai Lin
{"title":"Bisecting GlcNAc enhances CD8<sup>+</sup> T cell-mediated killing of breast cancer by suppressing PD-L1 expression and its binding to PD-1.","authors":"Xueting Ren, Jinpeng Wu, Jing Li, Zhen Zhai, Xiang Li, Feng Guan, Meng Wang, Xiaobin Ma, Zengqi Tan, Huafeng Kang, Shuai Lin","doi":"10.1186/s40164-025-00693-w","DOIUrl":"10.1186/s40164-025-00693-w","url":null,"abstract":"<p><strong>Background: </strong>The abundance of PD-L1 on the surface of tumor cells is a critical factor in sensitizing these cells to T cell-mediated immune killing. While abnormal glycosylation of PD-L1 is known to influence its expression and function, the precise regulatory mechanisms remain unclear.</p><p><strong>Methods: </strong>This study utilized bioinformatics analysis to explore the role of MGAT3, a key gene involved in the formation of the bisecting GlcNAc structure, in breast cancer (BC). Experimental approaches were employed to increase bisecting GlcNAc levels in BC cells, followed by assessments of PD-L1 expression, CD8<sup>+</sup> T cell-mediated cytotoxicity, extracellular vesicle (EV)-associated PD-L1, and PD-L1/PD-1 interaction. Additionally, forskolin, a bisecting GlcNAc agonist, was combined with anti-PD-L1 antibody to evaluate its antitumor effects in vivo.</p><p><strong>Results: </strong>MGAT3 was found to be expressed at low levels in BC tissues but positively correlated with CD8<sup>+</sup> T cell infiltration. Elevating bisecting GlcNAc levels in BC cells significantly enhanced the cytotoxic efficacy of CD8<sup>+</sup> T cells. High bisecting GlcNAc modification promoted PD-L1 degradation via the lysosomal pathway, reducing PD-L1 expression and its binding to PD-1. Furthermore, increased bisecting GlcNAc levels reduced PD-L1 in tumor cell-derived EVs, impairing the EVs' ability to block CD8<sup>+</sup> T cells and indirectly enhancing T cell cytotoxicity. The combined use of forskolin and anti-PD-L1 antibody significantly increased CD8<sup>+</sup> T cell abundance and activity, achieving a more effective antitumor response in vivo.</p><p><strong>Conclusions: </strong>These findings demonstrate that enhancing bisecting GlcNAc modification in BC cells promotes PD-L1 degradation and inhibits its binding to PD-1, thereby boosting CD8<sup>+</sup> T cell-mediated cytotoxicity, providing a promising strategy for immune modulation in BC therapy.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"102"},"PeriodicalIF":13.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783895","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
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
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