Neoplasia最新文献

{"title":"Hepatocellular carcinoma escapes immune surveillance through deceiving thymus into recalling peripheral activated CD8+ T cells","authors":"Qiaoting Hu ,&nbsp;Xuefeng Wang ,&nbsp;Yundan You ,&nbsp;Jun Liu ,&nbsp;Bin Lan ,&nbsp;Fangfang Chen ,&nbsp;Hong Wen ,&nbsp;Haili Cheng ,&nbsp;Weibin Zhuo ,&nbsp;Ting Xu ,&nbsp;Jingxian Zheng ,&nbsp;Yuchuan Jiang ,&nbsp;Xiaojie Wang ,&nbsp;Jing Lin ,&nbsp;Zengqing Guo ,&nbsp;Sha Huang ,&nbsp;Gang Chen ,&nbsp;Yu Chen ,&nbsp;Jingfeng Liu","doi":"10.1016/j.neo.2025.101210","DOIUrl":"10.1016/j.neo.2025.101210","url":null,"abstract":"<div><div>The role of thymic epithelial cells (TECs) in eliminating self-reactive T cells through the presentation of self-antigens is well-established. However, it remains unclear whether TECs can eliminate tumor-reactive CD8⁺ T cells by presenting tumor antigens. In this study, we observed that CD73⁺ Granzyme B⁺ peripheral activated CD8⁺ T cells undergo apoptosis in the medullary region of the thymus in DEN-CCL₄-induced spontaneous HCC mice, but not in the naïve control group. Mechanistically, HCC cells manipulate the thymus to recruit peripheral activated CD8⁺ T cells through the CCL19/CCL21-CCR7 axis. Additionally, TECs capture antigens from HCC cells for subsequent antigen presentation instead of <em>de novo</em> expressing tumor antigens. When tumor-associated CD8⁺ T cells homing to the thymus recognize the same tumor antigen presented by TECs, activation-induced cell death (AICD) is initiated in these T cells. Thymectomy redistributes CD8⁺ T cells into the tumor focus to suppress HCC growth. Alternatively, both inhibiting CCL19/CCL21 expression of thymic cells using an AMPK activator and blocking CCR7 on CD8⁺ T cells binding with ligands using Cmp2105 significantly reduces tumor-educated thymus dependent immune evasion. Our findings collectively demonstrate that HCC manipulates the thymus to trigger immune escape; pharmacologically targeting CCL19/CCL21-CCR7 axis to inhibit thymus homing can increase CD8⁺ T cells in the tumor microenvironment.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101210"},"PeriodicalIF":4.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The TRIM22-CDT2 axis is the key mediator of the p53-Rb signals in growth control of HPV-positive cervical carcinoma cells","authors":"Qing Zhou ,&nbsp;Hongfei Yu ,&nbsp;Anliang Dong ,&nbsp;Jiani Yi ,&nbsp;Jia Li ,&nbsp;Xufan Li ,&nbsp;Liyuan Zhou ,&nbsp;Qiongzi Qiu ,&nbsp;Bingjian Lu ,&nbsp;Honghe Zhang ,&nbsp;Weiguo Lu ,&nbsp;Yi Sun ,&nbsp;Pengyuan Liu ,&nbsp;Yan Lu","doi":"10.1016/j.neo.2025.101211","DOIUrl":"10.1016/j.neo.2025.101211","url":null,"abstract":"<div><div>Persistent infection with high-risk human papillomavirus (HPV) is the primary contributor to the development of cervical cancer. Although HPV oncoproteins E6 and E7 clearly trigger cervical tumorigenesis by inactivating p53 and Rb pathways, the downstream mediators of p53/Rb inactivation remain elusive. Here we report that CDT2, a subunit of Cullin-RING ligase 4 (CRL4), is significantly upregulated in cervical carcinoma tissues, which correlates with E6/E7 expression and poor patient survival. Mechanistically, E7-mediated Rb degradation upregulates E2F1, which in turn increases CDT2 transcription, whereas E6-mediated p53 degradation downregulates TRIM22, a novel E3 ligase for CDT2 degradation, leading to CDT2 accumulation to promote growth and survival of cervical cancer cells. Importantly, CDT2 depletion induces DNA aneuploidy and senescence via stabilization of histone lysine methyltransferase SET8, a CRL4^CDT2 substrate, acting as a tumor suppressor. Collectively, the TRIM22-CDT2-SET8 axis is the key mediator of the p53/Rb signals in regulation of growth and survival of HPV-positive cervical carcinoma cells, Thus, CDT2 could serve as a prognostic biomarker and therapeutic target for these carcinomas.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101211"},"PeriodicalIF":4.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biphasic behavior of T cell subsets reflects failure of early anti-myeloma response and leads to progressive T cell dysfunction","authors":"Suchita Suryakant Jadhav ,&nbsp;Vipin Sharma ,&nbsp;Aharon Lion ,&nbsp;Lasser-Katz Efrat ,&nbsp;Iftach Shaked ,&nbsp;Galia Luboshits ,&nbsp;Michael A. Firer","doi":"10.1016/j.neo.2025.101208","DOIUrl":"10.1016/j.neo.2025.101208","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple Myeloma (MM) progresses over 2-3 decades through two pre-malignant stages (MGUS and SMM), culminating in clinically active disease. Given the limitations in acquiring sequential bone marrow (BM) samples from patients over this time frame, the mechanisms that compromise immunosurveillance and promote the development of MM remain</div></div><div><h3>Methods</h3><div>Balb/c mice inoculated with MOPC315.BM myeloma cells were followed over the next 220 days. Blood and bone marrow samples were collected on days 80, 150, and 220 post cell inoculation. Blood samples were used to monitor levels of paraprotein and whole blood cell counts. BM aspirates were used for deep immune profiling by flow cytometry and for T cell function assays.</div></div><div><h3>Results</h3><div>Blood analyses validated that the model reflects serological features of human MM. Analysis of BM samples revealed a biphasic behavior of T regulatory cells, Th17 cells, CD8+ cytotoxic T cells and NK cells, as well as skewing of CD4+ and CD8+ T memory cell subset distributionss, suggesting failure of an early anti-myeloma response, which is replaced by progressive immunosuppression, and dysfunction and exhaustion of CD8+ T cell tumor cytotoxicity.</div></div><div><h3>Conclusion</h3><div>Our new model is a flexible tool to investigate the early cellular interactions that initiate immunosuppression and MM disease progression. The model can also be used to test the efficacy of new therapeutic strategies.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101208"},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The DNA mismatch repair protein, MSH6 is a novel regulator of PD-L1 expression","authors":"Kirsten Brooksbank ,&nbsp;Charlotte Smith ,&nbsp;Eleni Maniati ,&nbsp;Amy Gibson ,&nbsp;Wai Yiu Tse ,&nbsp;Amy Kate Hall ,&nbsp;Jun Wang ,&nbsp;Tyson V Sharp ,&nbsp;Sarah A Martin","doi":"10.1016/j.neo.2025.101207","DOIUrl":"10.1016/j.neo.2025.101207","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) are extremely effective in a subgroup of mismatch repair-deficient (MMRd) cancers, but ∼50% remain resistant to treatment. We have shown for the first time that this may be due to the differential regulation of factors linked to response to ICIs upon loss of the different MMR genes. Here, we show that increased PD-L1 expression is observed upon loss of the MMR genes MLH1, MSH2 and PMS2. However, this is not true upon loss of MSH6, and we show that this is due to a novel role for MSH6 as a direct regulator of PD-L1 transcription, dependent on recruitment by the histone trimethyltransferase SETD2. Next-generation sequencing of MLH1 and MSH6 knockout (KO) cells revealed that MSH6 KO cells have significantly lower microsatellite instability in comparison to MLH1 KO cells, despite MSH6 KO cells having a higher mutational burden. These findings emphasise the need for gene-specific stratification in the MMRd cohort.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101207"},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor neoantigens as key drivers of significant anti - tumor immunity in triple - negative breast cancer mouse models","authors":"Yujeong Her ,&nbsp;Jeong Yeon Kim ,&nbsp;Hocheol Shin ,&nbsp;Kwangmin Yu ,&nbsp;Kyu-Jin Lee ,&nbsp;Yi Rang Na ,&nbsp;Sangyong Jon ,&nbsp;Jung Kyoon Choi ,&nbsp;Hyeong-Gon Moon","doi":"10.1016/j.neo.2025.101205","DOIUrl":"10.1016/j.neo.2025.101205","url":null,"abstract":"<div><div>Recent studies have highlighted the therapeutic potential of targeting tumor neoantigens in solid tumors; however, its efficacy in breast cancer remains unclear. Here, we evaluate the impact of tumor neoantigen-targeted strategies in a syngeneic mouse mammary carcinoma model. Mice previously exposed to 4T1 tumor cells (PETCs) or treated with tumor cell-derived lysates (TdLs) exhibited robust antitumor immunity, leading to reduced tumor growth and metastasis through tumor immune microenvironment remodeling. TdL administration in mice harboring orthotopic tumors significantly enhanced the efficacy of immune checkpoint blockade, suggesting its potential as an immunotherapeutic adjuvant. To further optimize neoantigen-based approaches, we developed a lipid nanoparticle (LNP)-based delivery system for neoantigen peptides, which effectively suppressed tumor progression and metastasis in vivo. Mechanistically, this strategy promoted antigen-specific T cell activation and reshaped the tumor immune landscape, enhancing immune-mediated tumor rejection. These findings underscore the therapeutic promise of personalized tumor neoantigen-targeted immunotherapy in breast cancer and support its further evaluation in clinical settings.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101205"},"PeriodicalIF":4.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SKI regulates rRNA transcription and pericentromeric heterochromatin to ensure centromere integrity and genome stability","authors":"Víctor Pola-Véliz ,&nbsp;David Carrero ,&nbsp;Eduardo A. Sagredo ,&nbsp;Víctor Inostroza ,&nbsp;Claudio Cappelli ,&nbsp;Solange Rivas ,&nbsp;Mirit Bitrán ,&nbsp;Evelyn Zambrano ,&nbsp;Evelin Gonzalez ,&nbsp;Fernanda Morales ,&nbsp;Marcia Manterola ,&nbsp;Martín Montecino ,&nbsp;Ricardo Armisén ,&nbsp;Katherine Marcelain","doi":"10.1016/j.neo.2025.101204","DOIUrl":"10.1016/j.neo.2025.101204","url":null,"abstract":"<div><div>Accurate chromosome segregation and ribosomal gene expression silencing are essential for maintaining genome integrity, and disruptions in these processes are key for oncogenesis and cancer progression. Here, we demonstrate a novel role for the transcriptional co-repressor SKI in regulating rDNA and pericentromeric heterochromatin (PCH) silencing in human cells. We found that SKI localizes to the rDNA promoter on acrocentric chromosomes and is crucial for maintaining H3K9 trimethylation (H3K9me3) and repressing 45S rRNA gene expression. SKI is also associated with BSR and HSATII satellites within PCH, where is necessary for H3K9 methylation and recruitment of SUV39H1 and HP1α, key players for heterochromatin silencing and centromere function. Consequently, SKI deficiency disrupted centromere integrity and resulted in aberrant chromosome segregation, micronuclei formation, and chromosome instability. The identification of SKI as a key participant in the epigenetic-mediated silencing of pericentromeric and ribosomal DNA provides a fundamental insight, paving the way for new research into the intricate relationship between transcriptional regulation and genome instability during cancer progression, and opening novel opportunities for therapeutic intervention.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101204"},"PeriodicalIF":4.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMYD2 epigenetically activates BMP4/SMAD1/5/8/ID3 axis to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma","authors":"Shanshan Wang ,&nbsp;Weicheng Wu ,&nbsp;Zhen Shi ,&nbsp;Mei Bin ,&nbsp;Fengwei Zhang ,&nbsp;Long Cai ,&nbsp;Kaiqing Lin ,&nbsp;Zhihui Li","doi":"10.1016/j.neo.2025.101203","DOIUrl":"10.1016/j.neo.2025.101203","url":null,"abstract":"<div><h3>Background</h3><div>Drug resistance prominently hampers the effects of sorafenib in hepatocellular carcinoma (HCC). Epigenetics play important roles in drug resistance. However, the contributions of SET And MYND Domain Containing 2 (SMYD2) to sorafenib resistance in HCC remain unknown. This study is aimed at elucidating the role and mechanism of SMYD2 in sorafenib resistance of HCC.</div></div><div><h3>Methods</h3><div>Using our well-established sorafenib-resistant hepatocellular carcinoma (HCC) cell lines and xenograft mouse models, we evaluated SMYD2 expression levels. To investigate the biological functions of SMYD2, we conducted a series of functional assays <em>in vitro</em> and <em>in vivo</em>. Transcriptomic profiling via RNA sequencing (RNA-seq) was performed to identify downstream targets of SMYD2. Additionally, chromatin immunoprecipitation (ChIP) assays were employed to elucidate the molecular mechanism. Correlating SMYD2 and target gene expression patterns with clinical outcomes in HCC patients was investigated.</div></div><div><h3>Results</h3><div>SMYD2 expression was significantly elevated in sorafenib-resistant HCC cells compared with parental cells. Knockdown or overexpression of SMYD2 substantially inhibited or enhanced, respectively, HCC stemness and sorafenib resistance. Mechanistically, SMYD2 promoted BMP4 expression via the maintenance of mono-methylation of histone 3 lysine 4 (H3K4me1) and di-methylation of histone 3 lysine 36 (H3K36me2) modification of its promoter. Meanwhile, knockdown or inhibition of BMP4 suppressed the stemness of sorafenib-resistant cells, inhibited the activation of SMAD1/5/8 (R-SMADs), and decreased the expression of <em>inhibitor Of DNA binding 3 (ID3)</em> gene. Moreover, BMP4 addition or ID3 reconstruction can partly reverse the effect caused by repression of SMYD2 or BMP4. HCC patients with positive co-expression of SMYD2/BMP4 or SMYD2/ID3 or SMYD2/BMP4/ID3 exhibited the worst prognosis.</div></div><div><h3>Conclusions</h3><div>Our study reveals that SMYD2 is an important epigenetic mediator that activates BMP4/R-SMADs/ID3 axis, leading to enhanced stemness and sorafenib resistance. Thus, SMYD2 might represent a potential biomarker and future epigenetic therapeutic target for sorafenib resistance of HCC.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101203"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New horizons in B-cell lymphoma immunotherapy: From immune checkpoints to precision medicine","authors":"RuiXin Zheng ,&nbsp;YuXiao Li ,&nbsp;KaiXin Shi ,&nbsp;YuanYuan Pan ,&nbsp;KaiYi Liu ,&nbsp;JinCheng Song ,&nbsp;Li Li","doi":"10.1016/j.neo.2025.101206","DOIUrl":"10.1016/j.neo.2025.101206","url":null,"abstract":"<div><div>B-cell lymphoma, a malignancy in hematology with high heterogeneity, has its genesis and progression intricately associated with immune system regulation. Over the past three decades, transformative breakthroughs in B-cell malignancy investigations have emerged through paradigm-shifting molecular discoveries. Nevertheless, numerous hurdles persist in attaining a comprehensive understanding and effective treatment of this disease. Novel chemotherapeutic strategies demonstrate promising potential in B-cell lymphoma management, particularly through targeting immune checkpoints such as PD-1 (Programmed Cell Death Protein 1), LAG-3 (Lymphocyte-activation Gene 3), TIM-3 (T-cell Immunoglobulin and Mucin-domain containing-3), and TIGIT (T-cell Immunoreceptor with Ig and ITIM Domains) play pivotal regulatory roles within the immune system. These molecules critically orchestrate immune cell activation dynamics, proliferative capacity, and effector functions, thereby preserving immunological homeostasis. Deciphering the functional architecture of co-inhibitory checkpoints (e.g., PD-1/CTLA-4) in lymphomagenesis serves dual imperatives: deconstructing tumor immune evasion programs while establishing conceptual frameworks for precision immunotherapeutics development. PD-1 engagement with PD-L1/PD-L2 impairs T lymphocyte activation, facilitating tumor immune evasion. Deciphering these molecular processes enables therapeutic agents to employ targeted blockade strategies to restore antitumor immunity in lymphomas. Moreover, in-depth research on these checkpoints holds great promise for the discovery of novel biomarkers. These biomarkers may help predict responses to immunotherapy in lymphoma patients. This would enable clinicians to tailor personalized treatment plans for each patient, maximizing the therapeutic efficacy while minimizing unnecessary side-effects. Certain genetic signatures related to these immune checkpoints might be identified as predictors of a favorable response to PD-1 inhibitor-based immunotherapy. This analysis systematically deciphers the molecular interplay of PD-1/LAG-3/TIM-3/TIGIT immune checkpoint axes, delineating their regulatory dynamics in B-cell lymphomagenesis. It systematically summarizes the current research achievements, delves into the existing problems, and explores the future research directions. This approach seeks to advance dual contributions to fundamental science and clinical application in B-cell lymphoma immunotherapy, thereby facilitating therapeutic innovations while deepening mechanistic comprehension of disease pathogenesis. By doing so, it aims to provide valuable insights for both basic research and clinical translation in the field of B-cell lymphoma immunotherapy, ultimately enabling advancements in patient care and deeper insights into this multifaceted condition.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101206"},"PeriodicalIF":4.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immune response against cancer is modulated by stromal cell fibronectin","authors":"Alexander Lubosch ,&nbsp;Lauren Pitt ,&nbsp;Caren Zoeller ,&nbsp;Franziska Wirth ,&nbsp;Tarik Exner ,&nbsp;Barbara Steigenberger ,&nbsp;Guido Wabnitz ,&nbsp;Jutta Schroeder-Braunstein ,&nbsp;Inaam A. Nakchbandi","doi":"10.1016/j.neo.2025.101196","DOIUrl":"10.1016/j.neo.2025.101196","url":null,"abstract":"<div><div>Cancer-associated fibroblasts remain poorly understood, with some of them originating from the bone marrow. We therefore took advantage of the diversity of bone marrow stromal cells to shed light on how fibroblasts modulate cancer growth.</div><div>In two murine cancer models, adding these fibroblasts to tumor cells resulted in smaller lesions. Suppression was enhanced by pretreatment with fibronectin, while genetic deletion of fibronectin in a small subpopulation of stromal cells expressing osterix/<em>sp7</em> restored growth. The suppressive stromal population showed two more characteristics: the absence of CD31/<em>pecam1</em> and CD105/<em>endoglin</em>. However, only a decrease in CD105/<em>ENDOGLIN</em> in melanoma patients translated in improved survival. Mechanistically, fibronectin or fibronectin fragments activate integrin α5β1 and TLR4 and increase chemokine production by stromal cells ultimately leading to enhanced recruitment and activity of Ly6G⁺ myeloid cells without T-cell involvement.</div><div>This work thus characterizes a beneficial interaction between stromal cells and neutrophils enhancing the immune response against early cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101196"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCC","authors":"Chunli Zhang ,&nbsp;Limin Huang ,&nbsp;Zeyu Li ,&nbsp;Qian Wang ,&nbsp;Nanbin Liu ,&nbsp;Chongyu Zhang ,&nbsp;Xi Liu ,&nbsp;Chen Zhang ,&nbsp;Gaixia He ,&nbsp;Jin Sun ,&nbsp;Zongfang Li ,&nbsp;Hongwei Tian","doi":"10.1016/j.neo.2025.101198","DOIUrl":"10.1016/j.neo.2025.101198","url":null,"abstract":"<div><div>Tumors often evade immune surveillance by crippling their immunogenicity in the microenvironment. DHX34, an RNA helicase involved in nonsense-mediated mRNA decay pathway, is critical for aberrant RNA degradation. However, the effect of DHX34 in regulating the immunogenicity in hepatocellular carcinoma (HCC) is still unclear. Here, a surprising function of DHX34 in inhibited HCC immunogenicity is identified. DHX34-deficient tumors were infiltrated by activated T cells that impaired tumor growth and enhanced survival in mice. Mechanistically, DHX34 depletion triggered dsRNA accumulation which may activate cytosolic RNA-sensing pathway effectors such as <em>MAVS, p-IKK, p-IRF3</em>, and the subsequent type-I interferon response, evoking tumor-intrinsic immunity and leading to CD8 T activation. Collectively, DHX34 is implicated as a regulator that orchestrates a barrier in HCC by suppressing dsRNA-driven innate immune activation. Targeting DHX34 may enhance tumor immunogenicity and synergize with immunotherapies, offering a novel therapeutic strategy for HCC.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"67 ","pages":"Article 101198"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}