Journal of Hematology & Oncology最新文献

{"title":"Combination immunotherapy in hepatocellular carcinoma: synergies among immune checkpoints, TKIs, and chemotherapy","authors":"Suoyi Dai, Yuhang Chen, Wenxun Cai, Shu Dong, Jiangang Zhao, Lianyu Chen, Chien-Shan Cheng","doi":"10.1186/s13045-025-01739-6","DOIUrl":"https://doi.org/10.1186/s13045-025-01739-6","url":null,"abstract":"Combination therapy is rapidly becoming the cornerstone of hepatocellular carcinoma (HCC) treatment. Immune checkpoint inhibitors (ICIs) have emerged as a central strategy in systemic therapy, yet their efficacy as monotherapies remains limited. Consequently, combinatorial approaches, such as ICIs-Tyrosine kinase inhibitors (TKIs), ICIs-chemotherapy, and dual ICI regimens, are gaining momentum. While clinical trials have established efficacy benchmarks, mechanistic insights remain scarce, partly due to the limitations of current preclinical models in mimicking the complex tumor microenvironment (TME). Given the substantial heterogeneity of HCC, spanning genetic, transcriptomic, and immunologic dimensions, treatment outcomes vary widely. Additional factors such as gut microbiota and epigenetic modifications further influence therapeutic response and resistance. Although PD-1, PD-L1, and CTLA-4 inhibitors are widely used, unresponsiveness is common. Novel targets such as LAG-3, TIM-3, TIGIT, and VISTA, as well as strategies to reprogram fibrotic and immunosuppressive TME, are under active investigation. Ultimately, translating basic insights into personalized therapy will depend on predictive biomarkers and integrated analyses that account for the complex interactions among tumor cells, the immune system, and the TME. This review synthesizes current knowledge and cellular mechanisms underpinning combination therapies, highlights therapeutic synergies, and discusses emerging directions for stratified treatment in HCC. ","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"42 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of neoantigens and tumor mutational burden in cancer immunotherapy: advances, mechanisms, and perspectives","authors":"Shengbo Sun, Lanchun Liu, Jingkang Zhang, Liting Sun, Wenlong Shu, Zhengyang Yang, Hongwei Yao, Zhongtao Zhang","doi":"10.1186/s13045-025-01732-z","DOIUrl":"https://doi.org/10.1186/s13045-025-01732-z","url":null,"abstract":"Cancer immunotherapy has revolutionized oncology by leveraging the immune system to combat tumors. Among various biomarkers, neoantigens and tumor mutational burden (TMB) have emerged as critical factors in tailoring personalized treatments. Neoantigens are tumor-specific peptides displayed on cancer cell surfaces, derived from somatic mutations. Recognized as \"non-self\" by the immune system, they trigger T-cell responses and enable therapies like personalized vaccines and adoptive T-cell transfer. Critically, neoantigen potential correlates with TMB, which quantifies the total somatic mutations within a tumor genome. A higher TMB generally correlates with a greater likelihood of generating immunogenic neoantigens, making it a predictive biomarker for the efficacy of immune checkpoint inhibitors (ICI). Progress in high-throughput sequencing, bioinformatics, and immuno-peptidomics has significantly enhanced the accuracy of neoantigen prediction, including assessments of major histocompatibility complex (MHC) binding affinity and T-cell receptor recognition. Clinically, neoantigen-based therapies have shown efficacy in early trials, with strategies such as mRNA vaccines demonstrating synergy with ICI by boosting T-cell activation and overcoming immune suppression. Combining neoantigen-based therapies with chemotherapy and radiotherapy harnesses synergistic mechanisms to enhance efficacy, overcome resistance, and emerge as a pivotal oncology research focus. The integration of TMB into clinical practice has received regulatory approval as a biomarker for stratifying patients for ICI therapies. Furthermore, advanced methodologies like liquid biopsy and single-cell technologies have streamlined TMB measurement, improving its predictive value for personalized immunotherapy. Collectively, neoantigens and TMB have optimized the evolution of precision immuno-oncology by providing frameworks that maximize therapeutic efficacy, overcome resistance mechanisms, and advance durable cancer remission.​","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"31 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in S-palmitoylation and its emerging roles in human diseases","authors":"Juanjuan Shang, Mei Ding, Xiangxiang Zhou","doi":"10.1186/s13045-025-01738-7","DOIUrl":"https://doi.org/10.1186/s13045-025-01738-7","url":null,"abstract":"S-palmitoylation, one reversible post-translational modification (PTM) involving the binding of palmitate to proteins, influences protein stability, localization and interactions. Through S-palmitoylation, proteins can be targeted to specific cellular compartments, form functional complexes, and participate in intricate signaling cascades. Organized and reversible S-palmitoylation process achieves remarkable roles in the precise orchestration of biological activities, including cell signaling, membrane trafficking, synaptic transmission and cellular immunity. S-palmitoylation has been implicated in the pathogenesis of diverse disorders including cancers, cardiovascular diseases, metabolic diseases, immunological diseases, infection diseases, nervous system and mental diseases. Altered S-palmitoylation of proteins changes the oncogenic function, synaptic localization, enzymatic activity and signaling transduction, potentially contributing to disease progression. Understanding and targeting S-palmitoylation pathways hold promise for therapeutic interventions in associated diseases. Collectively, S-palmitoylation is a key regulatory mechanism with significant implications for disease pathogenesis. Investigating the role of S-palmitoylation provides insights into diagnostic markers and potential therapeutic targets, highlighting the importance of ongoing research in understanding the broader implications of S-palmitoylation in health and disease.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"13 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in universal chimeric antigen receptor T cell therapy","authors":"Ning Jiang, Zhaoyi Yang, Huilei Miao, Shujun Xing, Shuhang Wang, Ning Li","doi":"10.1186/s13045-025-01737-8","DOIUrl":"https://doi.org/10.1186/s13045-025-01737-8","url":null,"abstract":"While chimeric antigen receptor (CAR) T cell therapy is highly effective for hematological malignancies, its widespread use is limited by complex, patient-specific manufacturing. Universal CAR-T (UCAR-T) cells, derived from allogeneic donors, offer a potential \"off-the-shelf\" solution. However, their clinical translation hinges on overcoming two key immunological barriers: graft-versus-host disease (GvHD) and host-versus-graft rejection (HvGR), which compromise safety and therapeutic persistence. This review summarizes recent advances in UCAR-T cell engineering and clinical strategies designed to improve both safety and efficacy. We discuss gene-editing technologies—such as CRISPR/Cas9 and base editors—used to prevent GvHD by ablating the T cell receptor (TCR) and to evade HvGR by disrupting human leukocyte antigen (HLA) expression. We also explore the development of UCAR-T products from alternative cell sources with low intrinsic alloreactivity, such as γδ T cells. Furthermore, we detail multifaceted approaches to augment UCAR-T cell function and persistence, from the perspectives of enhancing intrinsic functions, reshaping the tumor microenvironment (TME) and overcoming tumor heterogeneity. Finally, we analyze recent clinical trial outcomes, which show promising efficacy in hematological malignancies but highlight ongoing challenges in solid tumors. The continued integration of sophisticated cellular engineering with innovative clinical strategies—such as enhanced lymphodepletion, combination therapies, and alternative administration routes—will be essential to realize the full potential of UCAR-T as a widely accessible and potent cell therapy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"29 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical applications of circulating tumor cells in metastasis and therapy","authors":"Chuan Yang, Can Liu, Chenglai Xia, Liwu Fu","doi":"10.1186/s13045-025-01733-y","DOIUrl":"https://doi.org/10.1186/s13045-025-01733-y","url":null,"abstract":"Circulating tumor cells (CTCs), which serve as an early indicator of tumors in peripheral blood, are closely associated with unfavorable prognoses in individuals with cancer. Gaining a thorough understanding of the heterogeneity and specific trajectory of CTCs during metastasis can yield valuable insights for the development of effective cancer treatment strategies. This review critically examines the contemporary knowledge of the in vivo process of CTCs, with a focus on the four key stages: dissemination, homing, colonization, and macro-metastasis. Each stage is discussed in terms of its associated characteristics, including epithelial-mesenchymal transition (EMT), dormancy, organotropism, and awakening. We also discuss recent advancements in CTC isolation, detection, cultivation and its potential applications. Additionally, it provides a comprehensive elucidation of the intricate mechanisms of immune evasion and drug resistance in CTCs, aiming to identify novel targets for cancer therapy. Finally, an overview of CTC interventions is presented, which may facilitate the development of personalized therapeutic approaches for patients and improve their metastasis-free prognostic outcomes.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges","authors":"Qianwen Liu, Jingfeng Li, Xiuqiao Sun, Jiayu Lin, Zhengwei Yu, Yue Xiao, Dan Li, Baofa Sun, Haili Bao, Yihao Liu","doi":"10.1186/s13045-025-01735-w","DOIUrl":"https://doi.org/10.1186/s13045-025-01735-w","url":null,"abstract":"Immunosenescence, the age-related decline in immune function, profoundly impacts cancer progression and therapeutic outcomes by fostering a tumor-promoting microenvironment and impairing immune surveillance. This review delineates eleven molecular hallmarks of immunosenescence, including genomic instability, telomere attrition, epigenetic dysregulation, mitochondrial dysfunction, and chronic inflammation, which collectively drive immune cell dysfunction and systemic immunosuppression. Aging reshapes the tumor microenvironment (TME) through recruitment of immunosuppressive cells, senescence-associated secretory phenotypes (SASP), and metabolic reprogramming, contributing to therapy resistance and poor prognosis in elderly patients. While immunotherapies such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell immunotherapy (CAR-T) cells show promise, their efficacy in aging populations is limited by T cell exhaustion, myeloid bias, and altered intercellular communication. Emerging strategies—including senolytics, epigenetic modulators (e.g., histone deacetylase (HDAC) inhibitor), and metabolic interventions (e.g., spermidine, nicotinamide mononucleotide (NMN))—highlight potential avenues to rejuvenate aged immunity. Single-cell multi-omics (single cell RNA-seq, single cell ATAC-seq) further unravel immune cell heterogeneity, revealing tissue-specific chromatin accessibility dynamics and novel targets like interleukin-34 (IL-34) for microglia-mediated neuroinflammation. However, challenges persist in translating preclinical findings to clinical practice, necessitating age-tailored trials and biomarker-driven approaches. By integrating mechanistic insights with translational innovations, this review underscores the urgency of addressing immunosenescence to optimize cancer immunotherapy for aging populations, ultimately bridging the gap between aging biology and precision oncology.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target neutrophil heterogeneity and plasticity in cancer","authors":"Ye Feng, Guang Liu, Haiqing Li, Lin Cheng","doi":"10.1186/s13045-025-01731-0","DOIUrl":"https://doi.org/10.1186/s13045-025-01731-0","url":null,"abstract":"Neutrophils have long been regarded as cells of a limited lifespan, known to produce pro-inflammatory molecules, and primarily engaged in combating infections. However, recent advancements in single-cell analysis and molecular biology have revealed their remarkable heterogeneity and plasticity, particularly within the context of tumors. This review explores the development and diversity of neutrophils under both physiological and pathological conditions, with a particular focus on their roles in cancer. The discussion encompasses the emergence of distinct neutrophil subtypes, particularly senescent neutrophils, within tumors and their context-dependent functions in tumorigenesis, progression, metastasis, and recurrence. The plasticity of these cells, driven by intrinsic factors and the tumor microenvironment, allows them to be reprogrammed between pro-tumor and anti-tumor phenotypes. This process is influenced by cytokines, metabolic reprogramming, and interactions with other immune cells. The potential of targeting and engineering neutrophil as a therapeutic avenue for cancer treatment is further underscored, including the use of senolytic agents, metabolic inhibitors, and reprogramming strategies. Finally, future research directions are proposed to further elucidate the mechanisms underlying neutrophil heterogeneity and plasticity, with the aim of developing novel therapeutic approaches to modulate neutrophil function in cancer.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"3 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitophagy’s impacts on cancer and neurodegenerative diseases: implications for future therapies","authors":"Jason Huang, Vincent Truong Pham, Shaozi Fu, Gang Huang, Ya-Guang Liu, Lei Zheng","doi":"10.1186/s13045-025-01727-w","DOIUrl":"https://doi.org/10.1186/s13045-025-01727-w","url":null,"abstract":"Substantial evidence supports an inverse relationship between cancer and neurodegenerative diseases (NDDs), but few studies investigate the biological mechanisms underlying this phenomenon. While previous explanations—such as inflammation, reactive oxygen species (ROS), genetic mutations, and cell death—remain significant, they ultimately converge on mitophagy. This review identifies mitophagy as a pivotal factor in the development of both cancer and NDDs, while also evaluating specific mechanisms and processes to clarify how mitophagy connects these opposing disease trajectories. By examining these factors, we aim to uncover the underlying mechanisms that explain the inverse relationship between cancer and NDDs, which will help develop therapeutic strategies that target common factors for both conditions.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"11 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications","authors":"Jinxin Tang, Yan Zhuang, Yibo Zhang, Hongkun Hu, Hua Wang, Haodong Xu, Yintao Li, Chao Tu","doi":"10.1186/s13045-025-01726-x","DOIUrl":"https://doi.org/10.1186/s13045-025-01726-x","url":null,"abstract":"Necroptosis represents a distinct form of programmed cell death that exhibits characteristics of both necrosis and apoptosis. Due to its potential to activate anti-cancer immune responses, utilizing necroptosis to enhance immune activity within the tumor microenvironment has garnered significant attention. However, effectively regulating necroptosis in cancer remains a formidable challenge. Epigenetic, post-transcriptional and post-translational modifications are three primary mechanisms that alter molecular expression patterns without changing DNA sequence, playing crucial roles in cancer progression. While these modifications have been shown to significantly influence cancer development, their specific roles in regulating necroptosis in cancer have not been systematically elucidated. This review explores the role and mechanism of epigenetic, post-transcriptional and post-translational modification in the regulation of necroptosis in cancer, identifying potential regulatory targets and their therapeutic implications, thereby providing systematic theoretical support for necroptosis as an emerging target for cancer therapy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"21 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CD276 with Adapter-CAR T-cells provides a novel therapeutic strategy in small cell lung cancer and prevents CD276-dependent fratricide","authors":"Beate Kristmann, Niels Werchau, Lakshmi Suresh, Elisabeth L. Pezzuto, Sophia Scheuermann, Simon Krost, Karin Schilbach, Moustafa Moustafa-Oglou, Anna-Sophia Mast, Miriam Droste, André Felsberger, Lukas Kiefer, Pierre Abramowski, Lars Zender, Joerg Mittelstaet, Christian M. Seitz","doi":"10.1186/s13045-025-01729-8","DOIUrl":"https://doi.org/10.1186/s13045-025-01729-8","url":null,"abstract":"Survival rates in Small Cell Lung Cancer (SCLC) remain dismal, posing a huge medical need for novel therapies. T-cells, engineered to express chimeric antigen receptors (CAR-T) have demonstrated clinical activity against a variety of haematological malignancies. Yet, efficacy against solid tumour entities remains limited. In this study, we investigated the expression of CD276 (B7-H3), an immune checkpoint molecule and promising target antigen for CAR-T therapy in SCLC, at the RNA and protein level. We further developed novel Fab-based adapter molecules (AM) targeting CD276 and optimized our previously established modular Adapter CAR-T (AdCAR-T) platform as well as AM dosing schemes. CD276 is broadly expressed across SCLC subtypes, representing a promising target for CAR-T therapy. We describe that T-cell activation and CAR-signalling induces CD276-expression on CAR-T, resulting in CD276-dependent fratricide, limiting anti-CD276-CAR-T expansion and activity. The AdCAR-T platform allows CAR-T expansion in absence of CD276 targeting. Novel CD276 targeted AMs demonstrate potent in vitro and in vivo activity against SCLC. Intermittent AM-dosing allows functional persistence of AdCAR-T in vivo in contrast to CD276-targeted conventional CAR-T. AdCAR-T in vivo expansion and activity is further promoted by introducing activation-induced, AM remote controlled, IL-18 secretion into the AdCAR-T design. We identified CD276 as a promising target antigen, uniformly expressed in SCLC and demonstrate the therapeutic potential of novel anti-CD276 Fab-based AM in combination with optimized, IL-18 armoured AdCAR-T.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"215 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}