Experimental Hematology & Oncology最新文献

{"title":"Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.","authors":"Jianqiang Yang, Catherine C Zhou, Soumya Vijaya Kumar, Chloe Shay, Yong Teng","doi":"10.1186/s40164-026-00795-z","DOIUrl":"10.1186/s40164-026-00795-z","url":null,"abstract":"<p><p>Metabolic reprogramming is a well-established hallmark of cancer, driven by oncogenic mutations and microenvironmental pressures to support rapid proliferation and adaptation to stress. This reprogramming is not uniform but instead exhibits profound metabolic heterogeneity, with distinct tumor subpopulations and spatial niches relying on divergent metabolic pathways such as glycolysis, oxidative phosphorylation, and nutrient scavenging. This heterogeneity evolves dynamically during tumor progression and in response to therapy, driven by genetic and epigenetic alterations, hypoxia, nutrient gradients, and therapeutic influences. Critically, it contributes to major clinical challenges by promoting immune evasion through nutrient competition and the accumulation of immunosuppressive metabolites, and by fostering therapy-tolerant cell states. A deeper understanding of the spatiotemporal dynamics of tumor metabolism and their functional consequences reveals novel therapeutic vulnerabilities. This review examines the origins and biological implications of metabolic heterogeneity, discusses strategies to overcome therapeutic resistance by targeting context-specific metabolic dependencies or by combining metabolic inhibitors with immunotherapy, and highlights the potential of patient stratification based on metabolic profiles. Ultimately, elucidating this metabolic complexity is essential for the development of innovative, personalized therapeutic approaches that improve outcomes in cancer treatment.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249741","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":"Engineered Salmonella delivering the NMDAR antagonist conantokin G synergizes with PD-L1 blockade to enhance colorectal cancer regression.","authors":"Solbi Kim, Sora Kang, Eunji Kim, Minju Han, Minchan Jeong, Jin-Man Kim, Heung Jin Jeon, Hyo-Jin Lee","doi":"10.1186/s40164-026-00794-0","DOIUrl":"10.1186/s40164-026-00794-0","url":null,"abstract":"<p><p>Engineered attenuated Salmonella typhimurium has been explored as a tumor-targeting platform for localized therapeutic delivery. Here, we developed a strain capable of secreting the N-methyl-D-aspartate receptor (NMDAR) antagonist conantokin G (Con G) via the flagellar type III secretion system (T3SS). The engineered bacteria preferentially accumulated in tumor tissues and induced robust colorectal cancer cell death characterized by membrane disruption, leading to significant tumor suppression in vitro and in vivo with minimal systemic toxicity. Bulk RNA-seq analysis confirmed induction of immunogenic cell death pathways and concurrent suppression of Treg-associated gene expression. Salmonella colonization was associated with increased tumor PD-L1 expression, likely driven by infection-induced inflammatory signaling, which provided a rationale for combination with α-PD-L1 therapy. Combination treatment enhanced tumor regression, prolonged survival, and achieved complete tumor clearance in a subset of mice. Analysis of 106 clinical colorectal cancer specimens further demonstrated that high expression of NR2B, a subunit of NMDAR, is associated with advanced disease stage and poor prognosis. Together, these findings establish NR2B as a clinically relevant therapeutic target and highlight engineered bacterial delivery of Con G as a strategy to sensitize colorectal cancer to immune checkpoint blockade.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257838","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":"Dual-target CAR-T cell therapy: latest updates from the 2025 ASH annual meeting.","authors":"Shi Feng, Ran Kong, Li Xiao, Xiangxiang Zhou","doi":"10.1186/s40164-026-00790-4","DOIUrl":"10.1186/s40164-026-00790-4","url":null,"abstract":"<p><p>Dual-target chimeric antigen receptor T (CAR-T) cell therapy has emerged as a promising strategy to address the key limitations of single-target CAR-T approaches, including antigen heterogeneity and antigen-negative escape. Recent studies have reported rapid progress in the engineering of dual-target CAR-T, incorporating diverse receptor architectures, logic-gated designs, and novel manufacturing platforms. Preclinical data demonstrate improved disease control across B-cell malignancies, acute myeloid leukemia, and autoimmune disease models. Here, we summarize the latest advancements in the preclinical investigations and clinical trials of dual-target CAR-T cell therapy presented at the 2025 ASH annual meeting.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239097","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":"Multifactorial effects of LGALS1 blockade sensitize tumors to immune checkpoint inhibitor.","authors":"Jessy John, Mohammad A I Al-Hatamleh, Monika Vashisht, Arpitha H Shivarudrappa, Huaibin Ge, Karen Siddoway, Anthony J Bragoli, Priya Singh, Mohamed Y Zaky, Dan P Zandberg, Qiyiwen Zhang, Mathias Danielsen, Marija Ciba, Tomáš Lášek, Balazs Schafer, Marvin H Caruthers, Yuefeng Gao, Xuedong Liu, Zhangguo Chen, Jing H Wang","doi":"10.1186/s40164-026-00784-2","DOIUrl":"10.1186/s40164-026-00784-2","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of all head and neck cancers. While immune checkpoint inhibitors (ICIs) have improved HNSCC outcomes, response rates remain low (10-20%). Identifying novel targets to sensitize HNSCC to ICI therapy is therefore a critical unmet clinical need.</p><p><strong>Methods: </strong>To identify potential new targets, we analyzed human HNSCC clinical samples and mouse HNSCC models. We evaluated blood-derived samples from ICI-treated HNSCC patients and tumor-bearing mice (responders vs. non-responders to anti-PD-L1 treatment). We tested the efficacy of combined LGALS1 inhibition and anti-PD-L1 therapy, characterizing immune profiles via flow cytometry. Additionally, we employed mechanistic assays to determine the effects of LGALS1 blockade on myeloid cell differentiation and CD8 T cell activation.</p><p><strong>Results: </strong>We showed that LGALS1 is upregulated in HNSCC in a subtype- and stage-dependent manner. Contrary to prior findings focusing on extracellular LGALS1, our study reveals that LGALS1 expression within SCC tumor cells, tumor-infiltrating myeloid cells, and activated CD8 T cells is predominantly intracellular. In mouse models, lower intracellular LGALS1 in myeloid cells and higher plasma LGALS1 levels correlated with anti-PD-L1 unresponsiveness; consistently, elevated serum LGALS1 predicted poor survival in ICI-treated HNSCC patients. Pharmacological LGALS1 inhibition sensitized tumors to anti-PD-L1 and markedly prolonged recipient survival. Notably, LGALS1 inhibition did not alter expression levels; instead, its efficacy depended on tumor-intrinsic and tumor-extrinsic mechanisms. The combination of LGALS1 blockade and anti-PD-L1 effectively remodeled the myeloid compartment, significantly decreasing the frequency of total CD11b⁺ cells and tumor-associated macrophages (TAMs) while shifting the remaining TAMs toward an M1-like phenotype. These changes, coupled with enhanced CD8 and CD4 T cell infiltration and effector function, promoted a less immunosuppressive tumor microenvironment. In vitro co-culture assays demonstrated that LGALS1 inhibition shifted TAM polarization toward an M1-like phenotype. Furthermore, LGALS1 blockade directly activated CD8 T cells via a STAT3-dependent mechanism.</p><p><strong>Conclusions: </strong>We conclude that LGALS1 possesses significant prognostic value for predicting ICI response in HNSCC. LGALS1 may represent a multimodal therapeutic target to sensitize tumors to immunotherapy, as its blockade simultaneously modulates tumor cells, myeloid cells, and CD8 T cells to overcome multi-layered resistance and promote robust anti-tumor immunity.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210694","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":"Statins enhance trastuzumab deruxtecan efficacy: preclinical synergy in HER2-negative models and clinical benefit in HER2-positive metastatic breast cancer.","authors":"Taha Koray Sahin, Cemal Orhan, Ibrahim Hanifi Ozercan, Harun Muglu, Besir Er, Arif Akyildiz, Salih Tunbekici, Ahmet Oruc, Musa Baris Aykan, Bahadir Koylu, Orhun Akdogan, Ilknur Deliktas Onur, Ozturk Ates, Ozan Yazici, Fatih Selcukbiricik, Nuri Karadurmus, Murat Araz, Dilek Erdem, Erdem Goker, Ahmet Bilici, Sercan Aksoy, Deniz Can Guven","doi":"10.1186/s40164-026-00787-z","DOIUrl":"10.1186/s40164-026-00787-z","url":null,"abstract":"<p><p>Trastuzumab deruxtecan (T-DXd) has demonstrated significant efficacy in metastatic breast cancer (mBC) with varying HER2 expression. Statins have been shown to increase HER2 membrane localization and stability, potentially enhancing responses to HER2-targeted therapies. We investigated whether statins enhance T-DXd activity through a translational approach combining a preclinical HER2-negative model and a real-world HER2-positive mBC cohort. In the preclinical arm, 60 female Wistar albino rats were induced with mammary tumors using N-methyl-N-nitrosourea (MNU). Animals were randomized into five groups: Control, MNU-only, MNU + T-DXd, MNU+statin, and MNU + T-DXd+statin. In the clinical arm, 109 patients with HER2-positive mBC who received T-DXd were retrospectively analyzed. The combination of T-DXd and statin significantly reduced tumor volume compared to either monotherapy (p < 0.0001) in a preclinical rat model. HER2 protein levels were found to be elevated in the statin and combination groups, as demonstrated by both IHC and Western blot analyses. In a real-world cohort of 109 heavily pretreated patients with HER2-positive mBC receiving T-DXd, concomitant statin use was associated with significantly improved median progression-free survival (mPFS) and median overall survival (mOS). Our findings revealed that statin use significantly enhanced the efficacy of T-DXd in both a preclinical HER2-negative rat model and patients with HER2-positive mBC. Prospective clinical trials are warranted to validate these observations.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204595","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":"Radiotherapy synergizes with CD24 blockade to initiate macrophage-driven systemic antitumor immunity in non-small cell lung cancer.","authors":"Gongjun Wang, Shuo Yuan, Fuhao Xu, Deli Mao, Tao Hu, Qixin Xu, Li Li, Zhihao Wei, Shuanghu Yuan","doi":"10.1186/s40164-026-00789-x","DOIUrl":"10.1186/s40164-026-00789-x","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy (RT) has been shown to elicit antitumor immune responses, yet it rarely induces durable systemic immunity. The identification of immune checkpoints that constrain RT-induced immune activation remains an unmet clinical need.</p><p><strong>Methods: </strong>Using genetic deletion, pharmacologic blockade, syngeneic bilateral and orthotopic murine non-small cell lung cancer (NSCLC) models, and single-cell RNA sequencing, we dissected the role of CD24 in RT-induced immune responses.</p><p><strong>Results: </strong>CD24 was overexpressed across NSCLC stages with stage-dependent bidirectional prognostic significance. CD24 exerted no tumor-intrinsic proliferative effects in vitro but drove macrophage-dependent immune evasion in vivo. Combined RT and CD24 blockade synergistically remodeled the tumor microenvironment-augmenting M1-polarised macrophages while suppressing M2 macrophages, regulatory T cells, and PMN-MDSCs-and induced reproducible abscopal responses across bilateral, orthotopic, and metastatic models regardless of radiation modality. Macrophage depletion abolished both local and distant tumor control, whereas CD8⁺ T cell depletion caused only partial attenuation, establishing macrophages as essential initiators of systemic immunity. Single-cell transcriptomics revealed that RT-induced CCL2 recruits peripheral CCR2⁺ monocytes that CD24 blockade reprograms into inflammatory macrophages; CCL2 neutralization completely abrogated the abscopal effect. Incorporating PD-1 blockade further amplified effector T cell responses and conferred durable tumor-specific immune memory.</p><p><strong>Conclusions: </strong>CD24 is a critical innate immune checkpoint restraining RT-induced systemic antitumor immunity. Combined RT, CD24 blockade, and PD-1 inhibition drives a macrophage-initiated, CCL2-CCR2-dependent innate-to-adaptive immune cascade, providing a mechanistic rationale for this combination strategy in NSCLC.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148994","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":"Long-term survival benefit of neoadjuvant oncolytic virus plus PD-1 blockade in acral melanoma: implications of STING in resistance and potential therapy.","authors":"Qian Zhao, Yu Du, Lifeng Li, Lili Mao, Xuan Wang, Zelong Xu, Jiayong Liu, Chuanliang Cui, Zhihong Chi, Xuan Gao, Kaihua Liu, Shuang Chang, Yan Kong, Xinan Sheng, Xuefeng Xia, Jun Guo, Jie Dai, Lu Si","doi":"10.1186/s40164-026-00786-0","DOIUrl":"10.1186/s40164-026-00786-0","url":null,"abstract":"<p><strong>Background: </strong>Our phase Ib neoadjuvant trial demonstrated that oncolytic virus (OV) combined with PD-1 blockade achieved a 77.8% pathological response rate and 81.5% 2-year relapse-free survival in patients with acral melanoma. Here, we report the sustained clinical efficacy from an extended 5-year follow-up and characterize the molecular determinants of resistance to inform a biomarker-driven combinatorial strategy.</p><p><strong>Methods: </strong>Thirty patients with resectable acral melanoma were enrolled and followed for 5-year survival. Pre- and post-treatment tumor tissues with matched blood samples were analyzed using integrated WES, WTS, TBS, and Olink proteomics. These multi-omic profiles were leveraged to delineate resistance mechanisms in non-responders, which were subsequently validated in murine melanoma models exploring STING agonist-based combination therapy.</p><p><strong>Results: </strong>At a median follow-up of 62.4 months, the 5-year relapse-free and overall survival rates were 70.7% (95% CI, 53.7-93.0%) and 80.0% (95% CI, 66.9-95.7%), respectively. Integrated multi-omics analyses revealed that non-responders, in contrast to responders, exhibited a failure in therapeutic remodeling of the tumor microenvironment. Specifically, non-responders were characterized by baseline innate immune suppression linked to STING pathway downregulation; low baseline STING expression significantly correlated with diminished immune infiltration and inferior clinical outcomes. In murine melanoma models, pharmacological activation of the STING pathway restored innate immune signaling and synergistically augmented the antitumor efficacy of OV plus PD-1 regimen.</p><p><strong>Conclusions: </strong>These data establish the durable long-term clinical benefits of neoadjuvant OV plus PD-1 blockade in acral melanoma. Our findings identify STING dysfunction as a key mediator of therapeutic resistance, providing a rational for integrating STING agonists to optimize the clinical efficacy of this combinatorial approach. Trial registration Retrospectively registered: NCT04197882, 2019-12-13.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143287","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":"Bidirectional crosstalk between cancer-associated fibroblasts and tumor immunity: shaping the microenvironment and response to immune checkpoint therapy.","authors":"Shiqing Wang, Di Wang, Yipeng Zhou, Wen Li, Guofu Sun, Lijuan Cao, Chao Feng, Yongjing Chen, Changshun Shao, Qi Gui, Peishan Li, Yufang Shi, Jiankai Fang","doi":"10.1186/s40164-026-00783-3","DOIUrl":"10.1186/s40164-026-00783-3","url":null,"abstract":"<p><p>Immune checkpoint therapy (ICT) has revolutionized cancer treatment by restoring cytotoxic T-cell activity, yet primary and acquired resistance remain pervasive. Increasing evidence reveals that such resistance is not dictated solely by tumor-intrinsic factors but arises from the dynamic interplay between malignant and stromal compartments within the tumor microenvironment. Among these, cancer-associated fibroblasts (CAFs)-the dominant stromal population-have emerged as key orchestrators of immune accessibility and therapeutic outcome. Beyond forming structural barriers through extracellular matrix remodeling, CAFs actively shape immune cell recruitment, polarization, and effector functions via diverse cytokines, chemokines, and metabolic pathways. In turn, immune-derived mediators reprogram CAF states, establishing bidirectional feedback circuits that continuously recalibrate stromal and immune homeostasis. These reciprocal networks transform the immune microenvironment into a self-adaptive ecosystem that governs tumor progression and responsiveness to ICT. This review synthesizes recent advances in understanding CAF-immune crosstalk, emphasizing how such interactions drive both primary and acquired resistance to checkpoint blockade. We further highlight emerging therapeutic strategies aimed at reprogramming the CAF-immune axis-rather than eradicating it-to restore durable and systemic antitumor immunity.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137047","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":"Emerging therapeutic advances for immune thrombocytopenia: highlights from selected early‑phase and pivotal trials at the 2025 ASH annual meeting.","authors":"Linyu Cao, Zhe Wang, Qian Xiang","doi":"10.1186/s40164-026-00781-5","DOIUrl":"10.1186/s40164-026-00781-5","url":null,"abstract":"<p><p>This letter highlights emerging immune-targeted therapies for immune thrombocytopenia (ITP) presented at the 2025 ASH Annual Meeting. We summarize pivotal data, including the Phase III VAYHIT2 trial of Ianalumab, alongside novel early-phase agents targeting BAFF-R, CD38, CD19, PI3K, and cellular therapies (CD19/BCMA CAR-T), which provide crucial biological insights and hypothesis-generating signals for future ITP management.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13217741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053714","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":"Preclinical and clinical studies on CAR-NK cell therapy: latest update from 2025 ASH Annual Meeting.","authors":"Hanxi Luo, Yiyang Ding, Xiangyu Zhao","doi":"10.1186/s40164-026-00780-6","DOIUrl":"10.1186/s40164-026-00780-6","url":null,"abstract":"<p><p>Chimeric antigen receptor-engineered natural killer (CAR-NK) cells are emerging as an off-the-shelf immunotherapy for hematologic malignancies, supported by early clinical data and a favorable safety profile. Compared with CAR-T therapy, CAR-NK cells offer the potential for scalable allogeneic manufacturing with reduced toxicity while retaining antitumor activity. However, challenges such as limited in vivo persistence, immunosuppressive tumor microenvironments, and variable durability of responses remain. This summary highlights recent preclinical and clinical advances in CAR-NK cell therapy reported at the 2025 ASH Annual Meeting, focusing on engineering strategies to enhance NK-cell fitness and early trial results demonstrating efficacy with manageable toxicity.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"15 1","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971824","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}