Cellular Oncology最新文献

{"title":"COPB2 facilitates EDEM3-mediated mannose trimming to sustain ER homeostasis in ovarian cancer.","authors":"Dong-Xue Li, Ni Yang, Lan-Yu Hua, Jun-Jie Wang, Dilinazi Abudujilile, Zhi-Gang Zhang, Peng-Feng Zhu, Ting-Yan Shi, Rong Zhang","doi":"10.1007/s13402-025-01089-y","DOIUrl":"https://doi.org/10.1007/s13402-025-01089-y","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a lethal gynecologic malignancy with limited therapeutic success due to late diagnosis and therapy resistance. Endoplasmic reticulum (ER) stress and ER-associated degradation (ERAD) are key to tumor adaptation, yet the mechanisms sustaining ER homeostasis in OC remain poorly defined.</p><p><strong>Methods: </strong>We combined multi-omics analyses, tissue microarrays, and in vitro and in vivo models. Functional assays involved COPB2 knockdown or overexpression in OC cells, xenografts in nude mice, and mechanistic studies including protein interaction and glycoproteomic analyses.</p><p><strong>Results: </strong>COPB2 was significantly upregulated in OC and associated with poor prognosis. It promoted cell proliferation and survival by alleviating ER stress and suppressing apoptosis. Mechanistically, COPB2 interacted with EDEM3, a key ERAD enzyme, enhancing its ER localization and mannose-trimming function. COPB2 depletion impaired EDEM3 activity, resulting in glycan processing defects and ER stress accumulation. In vivo, COPB2 overexpression accelerated tumor growth.</p><p><strong>Conclusions: </strong>This study identifies a novel COPB2-EDEM3 axis that maintains ER homeostasis and drives OC progression. Targeting this axis may offer new opportunities for therapeutic intervention and biomarker development.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741308","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":"SOX4 mediates cancer-associated fibroblasts related radioresistance in hepatocellular carcinoma.","authors":"Ke Jiang, Botian Huang, Shasha He, Meiyan Zhu, Xiao Zhao, Miaowen Liu, Zhenwei Peng, Yan Wang, Yong Chen","doi":"10.1007/s13402-025-01088-z","DOIUrl":"https://doi.org/10.1007/s13402-025-01088-z","url":null,"abstract":"<p><strong>Purpose: </strong>Cancer-associated fibroblasts (CAFs), a crucial component of tumor microenvironment, play a critical role in tumorigenesis, progression, and conferring resistance to radiotherapy and chemotherapy. This study aimed to investigate the association between CAFs, CAF- related genes, and radioresistance in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>CAFs were isolated from HCC tissues and subsequently utilized for co-culturing with HCC cells using CAFs-conditioned medium. An orthotopic HCC mouse model was established by co-implanting CAFs and HCC cells. Through integrative analysis of three RNA-sequencing datasets (TCGA-LIHC tumor vs. normal tissues, Huh7 radioresistant vs. parent cells, and CAF vs. control group), CAF-associated prognostic genes were identified using comprehensive bioinformatics approaches. Experimental validation was performed by real-time quantitative PCR, western blot, immunohistochemistry, cell viability assays, and colony formation assays.</p><p><strong>Results: </strong>Our findings demonstrated that CAFs significantly enhance radioresistance in HCC. Based on 13 CAF-related prognostic genes, TCGA-LIHC patients were stratified into two distinct clusters via consensus clustering, exhibiting significant differences in overall survival, immune cell infiltration, and therapeutic response. A prognostic nomogram incorporating three hub genes and clinical characteristics was developed. Notably, SOX4 was upregulated in tumor tissues, radioresistant cells, and CAF-exposed HCC cells, correlating with poor prognosis. SOX4 knockdown suppressed HCC proliferation and reversed CAF-induced radioresistance. Additionally, a competitive endogenous RNA (ceRNA) network of LINC00665/miR-122-5p/SOX4 was constructed.</p><p><strong>Conclusion: </strong>CAFs serve as crucial mediators of radioresistance in HCC, and CAF-related genes provide valuable prognostic and therapeutic insights. SOX4 emerges as a promising therapeutic target to improve radiotherapy efficacy in HCC.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741309","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":"Targeting CSPG4 enhances the anti-tumor activity of CAR-NK cells for glioblastoma.","authors":"Qi Xiong, Beibei Yin, Hong Jiang, Yusha Qiu, Gang Shi, Jia Xu, Tong Xu, Hongxin Deng","doi":"10.1007/s13402-025-01095-0","DOIUrl":"https://doi.org/10.1007/s13402-025-01095-0","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastoma (GBM), an aggressive brain malignancy with high recurrence rates and suboptimal response to conventional therapies, necessitates novel treatment strategies. Chimeric antigen receptor natural killer (CAR-NK) cell therapy represents a promising immunotherapeutic approach. CSPG4 (chondroitin sulfate proteoglycan 4), a tumor-associated antigen overexpressed in GBM and critically involved in tumor proliferation and metastasis, was investigated as a therapeutic target. This study aimed to evaluate the efficacy of CSPG4-targeted CAR-NK cells in GBM treatment.</p><p><strong>Methods and results: </strong>We engineered a second-generation CAR construct incorporating the CSPG4-specific scFv 763.74, a CD8 transmembrane domain, and intracellular co-stimulatory/activation domains from CD28 and CD3ζ. The resulting CAR-NK cells were tested for anti-tumor activity in vitro and in vivo. Results demonstrated that CSPG4-directed CAR-NK cells selectively recognized and lysed CSPG4-positive GBM cells, significantly suppressing tumor growth in preclinical models compared to control NK cells. Mechanistic studies confirmed that cytotoxicity was mediated through specific CSPG4 antigen engagement.</p><p><strong>Conclusion: </strong>CSPG4-targeted CAR-NK cells exhibit potent anti-GBM activity, highlighting their potential as a novel immunotherapy. These findings provide a robust preclinical foundation for advancing CSPG4-directed CAR-NK cell therapy into clinical trials, addressing the urgent need for effective treatments in GBM management.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728281","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":"Apo10 and TKTL1 in blood macrophages as non-invasive biomarkers for early detection of cervical cancer.","authors":"Shuqing Wang, Zhiying Mao, Yuying Liu, Chunyan Lan, Lizhi Liu, Musheng Zeng, Chuanbo Xie","doi":"10.1007/s13402-025-01092-3","DOIUrl":"https://doi.org/10.1007/s13402-025-01092-3","url":null,"abstract":"<p><strong>Purpose: </strong>Apo10 and TKTL1 are tumor-associated markers reflecting impaired apoptosis and enhanced glycolysis respectively. This study aimed to evaluate the diagnostic potential of Apo10, TKTL1, and APT (a combination of Apo10 and TKTL1) in screening early-stage cervical cancer.</p><p><strong>Methods: </strong>A total of 152 patients with cervical cancer and 152 age-matched healthy controls were enrolled at Sun Yat-sen University Cancer Center from November 2020 to August 2023. Clinical data were collected from the Hospital Information System (HIS) and medical records, and blood samples were collected from all participants before treatment using epitope detection in monocytes (EDIM) technology 60 min after their last meal. Descriptive statistics and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance of Apo10, TKTL1, and APT to those of conventional cervical cancer biomarkers (CEA, CA125, and SCC-A).</p><p><strong>Results: </strong>Most of the enrolled patients with cervical cancer had early-stage disease (70%) and squamous cell histology (84.9%). The Apo10, TKTL1, and APT levels were significantly higher in the cervical cancer group than in the control group (Apo10:139 vs. 132, TKTL1:121 vs. 114, APT: 260 vs. 246). We also found that Apo10, TKTL1, and APT showed superior diagnostic performance (AUC: 0.864, 0.865, 0.905) compared to traditional markers (CEA: 0.690, CA125: 0.594, SCC-A: 0.806). Sensitivity analysis revealed APT maintained high diagnostic value across tumor stages and in both HPV-negative (AUC = 0.967) and TCT-negative (AUC = 0.958) subgroups.</p><p><strong>Conclusion: </strong>Apo10, TKTL1, and APT outperform conventional biomarkers in detecting cervical cancer and may serve as reliable diagnostic indicators.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728280","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":"Fibroblast-derived PI16 enhances tumor immune-suppressive microenvironment via inducing Tregs differentiation.","authors":"Daqin Suo, Lily Liang, Zengfei Xia, Ying Zhang, Tingting Zeng, Shuangjiang Li, Xin-Yuan Guan, Yan Li","doi":"10.1007/s13402-025-01090-5","DOIUrl":"https://doi.org/10.1007/s13402-025-01090-5","url":null,"abstract":"<p><strong>Purpose: </strong>Esophageal squamous cell carcinoma (ESCC) is aggressive with a poor prognosis. The tumor microenvironment (TME) significantly affects tumor progression and therapy resistance. Previous work has shown that fibroblasts in metastatic lymph nodes can confer cisplatin resistance to ESCC cells via PI16 (peptidase inhibitor 16). This study investigates the role of fibroblast-derived PI16 in the ESCC TME.</p><p><strong>Methods: </strong>Public single-cell RNA sequencing (scRNA-seq) data for ESCC were analyzed. A cell co-culture assay was performed to evaluate regulatory T cells (Tregs) differentiation from naïve CD4⁺ T cells. Immunoprecipitation and mass spectrometry examined PI16's mechanism in Treg differentiation. In vitro and in vivo assays were conducted to explore fibroblast-derived PI16's function. Additionally, multiplex fluorescent immunohistochemistry (mfIHC) was performed.</p><p><strong>Results: </strong>Analyses of the scRNA-seq dataset (GSE203115) reveal that fibroblasts can be classified into PI16 ⁺ and PI16^- subclusters based on PI16 expression levels. PI16 induces Treg differentiation from naïve CD4⁺ T cells through a DOCK2-dependent mechanism. Treatment with a DOCK2 inhibitor significantly inhibits PI16-induced Treg differentiation and increases Teff cell infiltration in vivo. Moreover, upregulation of PI16 in the tumor stroma is associated with poorer long-term survival outcomes in patients with ESCC.</p><p><strong>Conclusions: </strong>PI16⁺ fibroblasts promote the differentiation of Tregs from naïve CD4⁺ T cells through interaction with DOCK2. Upregulation of PI16 in the tumor stroma is associated with poorer long-term survival outcomes in patients with ESCC. Given the accumulating evidence on the therapeutic impact of targeting the TME, PI16⁺ fibroblasts emerge as a promising novel therapeutic target to overcome tumor immune suppression.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689019","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":"A diagnostic model based on transcriptomic analysis reveals inflammation as a potential prognosis factor for hepatoblastoma with hepatocellular carcinoma features.","authors":"Yuhua Shan, Min Zhang, Hongxiang Gao, Lei Zhang, Chenjie Xie, Jiquan Zhou, Liyuan Yang, Ji Ma, Qiuhui Pan, Zhen Zhang, Min Xu, Song Gu","doi":"10.1007/s13402-025-01077-2","DOIUrl":"https://doi.org/10.1007/s13402-025-01077-2","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatoblastoma (HB) with hepatocellular carcinoma (HCC) features (HBHF) is a rare liver malignancy. Due to its rarity and diverse histological presentations, the prognosis of HBHF remains controversial, and diagnostic differentiation poses significant challenges. To enable more accurate outcome evaluation and targeted therapeutic strategies, rapid, comprehensive, and cost-effective methods are needed to complement histopathological evaluation.</p><p><strong>Methods: </strong>In this study, we conducted transcriptomic profiling on an HBHF cohort from our center and developed a machine-learning algorithm to quantify HCC-like expression features in HB tumors. Given overlapping histopathological and molecular charateristicss between HBHF and HCC, we further investigated shared risk factors associated with HBHF prognosis.</p><p><strong>Results: </strong>Significantly poorer outcomes in HBHF patients suggest fundamental biological distinctions from classical HB. Transcriptomic analysis revealed comparable somatic mutation profiles between HB and HBHF cohorts but identified inflammation activation, rather than specific mutations, as a key high-risk factor in HBHF. Clinical outcomes aligned with risk stratification generated by our quantification model.</p><p><strong>Conclusions: </strong>HBHF represents a distinct transitional entity between HB and HCC, exhibiting markedly worse clinical outcomes than HB. Our transcriptome-based computational model effectively discriminates HBHF and predicts its prognostic risk. Importantly, inflammatory activation emerges as a critical driver of tumor aggressiveness in this subtype.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625465","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":"S100A9 promotes resistance to anti-PD-1 immunotherapy in hepatocellular carcinoma by degrading PARP1 and activating the STAT3/PD-L1 pathway.","authors":"Xianwei Zhou, Chu Qiao, Xuehui Chu, Yajing Yang, Haoran Man, Jingxin Liu, Yunzheng Li, Zhu Xu, Huan Li, Xiaodong Shan, Zaowu Lian, Yanjun Lu, Weihong Wang, Decai Yu, Xitai Sun, Binghua Li","doi":"10.1007/s13402-025-01087-0","DOIUrl":"https://doi.org/10.1007/s13402-025-01087-0","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (PD-1) immunotherapy, have emerged as promising treatments for advanced hepatocellular carcinoma (HCC), significantly improving clinical outcomes. However, resistance to ICIs remains a major challenge, and the underlying mechanisms of this resistance are not yet fully understood. This study aimed to investigate the role of S100 calcium-binding protein A9 (S100A9) in mediating resistance to anti-PD-1 therapy.</p><p><strong>Approach and results: </strong>We conducted RNA sequencing (RNA-seq) on tumor samples from anti-PD-1 responders and non-responders in HCC patients. Differential expression analysis identified S100A9 as a potential driver gene of resistance to anti-PD-1 therapy. Subcutaneous tumor models and an orthotopic HCC model established via hydrodynamic transfection were utilized to evaluate the impact of S100A9 on the efficacy of PD-1 therapy. Our findings revealed that S100A9 promotes resistance to anti-PD-1 therapy in HCC. Mechanistically, S100A9 directly interacted with PARP1 and induced its degradation via the ubiquitin-proteasome pathway. This process increased STAT3 phosphorylation at Tyr705, thereby enhancing PD-L1 transcription. Notably, treatment with the S100A9 inhibitor Tasquinimod significantly improved the efficacy of anti-PD-1 therapy in HCC.</p><p><strong>Conclusions: </strong>Our study reveals that S100A9 facilitates immune evasion in HCC by enhancing PARP1 ubiquitination, STAT3 phosphorylation, and PD-L1 expression. Furthermore, combining S100A9 inhibitors with anti-PD-1 antibodies markedly enhances the therapeutic efficacy of ICIs in HCC. These findings highlight S100A9 as a potential therapeutic target for overcoming resistance to immunotherapy in HCC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625466","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":"EGFR blockade confers sensitivity to pan-RAS inhibitors in KRAS-mutated cancers.","authors":"Junling Han, Bo Yu, Jianan Jing, Xiaoyu He, Yunfen Hua, Guotai Xu","doi":"10.1007/s13402-025-01075-4","DOIUrl":"https://doi.org/10.1007/s13402-025-01075-4","url":null,"abstract":"<p><strong>Introduction: </strong>KRAS is one of the most commonly occurring mutated oncogene in human cancers. Development of KRAS G12C or G12D inhibitors exhibit promising clinical activities, but patients harboring other hotspot KRAS mutations cannot benefit from those strategies. Recent development in pan-RAS inhibitors have broad therapeutic implications and merit clinical investigation. However, intrinsic and acquired drug resistance caused by tumor heterogeneity greatly limit the clinical application, posing a significant challenge in this field.</p><p><strong>Results: </strong>In this study, through CRISPR/Cas9 sgRNA screening using a human kinome sgRNA library, EGFR was discovered to correlate with the sensitivity of KRAS-mutated tumors to pan-RAS inhibitor RMC-7977. Through multiple in vitro cell proliferation or viability assays, EGFR loss or pharmacological EGFR inhibition significantly enhances the effectiveness of pan-RAS inhibitors in multiple KRAS^G12C or KRAS^G12D cancer cell lines, disregarding their cellular origins. Mechanistically, co-inhibition of EGFR and pan-RAS may further dampen the RTK-RAS-RAF-MEK-ERK pathway activation than either alone, thereby enhancing the anti-tumor activity of pan-RAS inhibitors. Strikingly, with the LL/2 syngeneic mice tumor model, the combination of pan-RAS inhibitors and EGFR inhibitors demonstrated more significant in vivo therapeutic efficacy compared to either single agent.</p><p><strong>Conclusion: </strong>In conclusion, this study employed high-throughput CRISPR/Cas9 sgRNA screening to identify the enhanced anti-cancer effects when combining EGFR inhibitors with pan-RAS inhibitors in multiple human KRAS-mutated cancer cell lines as well as a mouse syngeneic tumor model. This synergy underscores the potential for a combinational therapy strategy, leveraging EGFR and pan-RAS inhibitors to improve treatment outcomes for patients with KRAS-driven cancers.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599549","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":"Single-cell and bulk transcriptome analysis identifies B-cell subpopulations and associated cancer subtypes with distinct clinical and molecular characteristics.","authors":"Yin He, Li Zhao, Yufen Zheng, Xiaosheng Wang","doi":"10.1007/s13402-025-01082-5","DOIUrl":"https://doi.org/10.1007/s13402-025-01082-5","url":null,"abstract":"<p><strong>Backgroud: </strong>Previous studies have identified B cell subpopulations with pro- and anti-tumoral activities, while the clinical relevance of B cell subpopulations-specific markers in pan-cancer remains understudied.</p><p><strong>Methods: </strong>We integrated 14 scRNA-seq datasets (102,504 cells from 424 patients, 15 cancer types) to identify B cell subpopulations via unsupervised clustering. We characterized their functional dynamics and prognostic relevance through analyzing single-cell, bulk and spatial transcriptomic data. Moreover, using B cell subpopulations-specific gene signatures, we constructed models for predicting cancer prognosis and immunotherapy response.</p><p><strong>Results: </strong>We identified eight B cell subpopulations (b00-b07) which were classified into naive, plasma, memory, germinal center (GC), and cycling B cells. Trajectory analysis revealed b02-naive and b04-GC cells in early phases, evolving into b01- and b03-plasma/b05- and b06-memory/b07-cycling and b05-memory subpopulations. Anti-tumor responses were activated in early pseudotime, complement/immunoglobulin pathways peaked in mid-pseudotime, and energy metabolism increased in late-pseudotime. The enrichment of b07-cycling and b04-GC was negatively correlated with cancer prognosis, while b02-naive had a positive correlation. Spatial transcriptomic analysis showed clustered b00-b06 versus dispersed b07 cells, with b04-GC and b07-cycling cells distant from tertiary lymphoid structure cores. Based on the expression profiles of 1,047 B cell subpopulations-specific signatures, we identified three pan-cancer subtypes with distinct clinical and molecular characteristics. Using 13 B cell subpopulations-specific signatures, we constructed models to accurately predict cancer survival outcomes and immunotherapy response.</p><p><strong>Conclusions: </strong>Our study delineates eight B cell subpopulations with distinct prognostic relevance. Signature-based stratification and models underscore their clinical relevance in cancer outcomes and therapy response, advancing understanding of B cell heterogeneity in cancer.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315964","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":"Lactylation: the regulatory code of cellular life activity and a barometer of diseases.","authors":"Xuebing Xu, Xuming Wu, Dandan Jin, Jie Ji, Tong Wu, Mengxiang Huang, Junpeng Zhao, Zihan Shi, Lirong Zhou, XuYang He, Yuxuan Huang, Shihai Xuan, Mingbing Xiao, Xiaolei Cao","doi":"10.1007/s13402-025-01083-4","DOIUrl":"https://doi.org/10.1007/s13402-025-01083-4","url":null,"abstract":"<p><p>Lactylation is a novel post-translational modification of proteins, which has attracted extensive attention since its discovery. Lactylation takes lactate, a common metabolite, as its substrate and mediates the modification under the action of lactyltransferases. Although lactylation modification was initially found to undergo in histones, subsequent studies have shown that this novel modification is not limited to specific protein classes, and can undergo in both histone and non-histone proteins. Lactylation has been proved to play an important regulatory role in a variety of diseases, including tumors, metabolic disorders, cardiovascular diseases, and neurodegenerative diseases. Given the tumor properties of its substrate lactate, lactylation has been most extensively studied in tumors, and as a result, we have gained a deeper understanding of the potential molecular mechanisms and regulatory roles of lactylation in tumors. In this paper, we will summarize the regulatory and functional mechanisms of lactylation, explain the cellular processes in which lactylation is involved and its association with various diseases, and look forward to the future clinical application of lactylation.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301190","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}