Translational Oncology最新文献

{"title":"CTSB-positive tumor-associated macrophages shape prognosis and therapeutic response in lung adenocarcinoma","authors":"Caiqiang Zhu ,&nbsp;Liang Liang ,&nbsp;Ning Xue ,&nbsp;Dan Mei ,&nbsp;Meng Tian ,&nbsp;Zhaoyue Zhang ,&nbsp;Xinchen Sun ,&nbsp;Xiaofeng Ding","doi":"10.1016/j.tranon.2026.102671","DOIUrl":"10.1016/j.tranon.2026.102671","url":null,"abstract":"<div><h3>Background</h3><div>Lung adenocarcinoma (LUAD) remains a major clinical challenge in assessment of clinical outcomes and therapeutic response. Although tumor-associated macrophages (TAMs) are known as crucial regulators of tumor progression, their heterogeneity and prognostic relevance in LUAD have not been fully elucidated.</div></div><div><h3>Methods</h3><div>The heterogeneity of TAMs was detected by integration analyses of single-cell data and spatial transcriptome data. The CTSB⁺ TAM-related signature (CTRS) was developed by machine learning algorithms across four LUAD datasets. Multi-omics analysis and functional experiments were applied to uncover the potential role and mechanism of CTSB⁺ TAMs in LUAD.</div></div><div><h3>Results</h3><div>Single-cell analysis identified CTSB⁺ TAM as a crucial player in LUAD progression with poor prognosis. The spatial co-localization of CTSB⁺ TAMs and tumor cells was confirmed on LUAD slides. Our proposed CTRS was generated and validated in four independent LUAD cohorts, with high scores indicating unfavorable outcomes Furthermore, high CTRS scores were correlated with immunosuppressive status, and poor responses to immune checkpoint blockade. Functional experiments demonstrated the role of CTSB⁺ TAMs in boosting proliferation and migration in LUAD cells.</div></div><div><h3>Conclusion</h3><div>Our research develops CTRS with reliable performance in evaluating patient clinical outcomes in LUAD, highlighting its potential utility in clinical decision-making.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102671"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947978","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":"Five-year survival of patients with non-small cell lung cancer treated with alkalization therapy","authors":"Shion Kachi ,&nbsp;Kazuyuki Suzuki ,&nbsp;Reo Hamaguchi ,&nbsp;Ryoko Narui ,&nbsp;Hiromasa Morikawa ,&nbsp;Hiromi Wada","doi":"10.1016/j.tranon.2026.102677","DOIUrl":"10.1016/j.tranon.2026.102677","url":null,"abstract":"<div><div>Acidic tumor microenvironments promote malignant progression, immune evasion, and drug resistance. This single-center retrospective cohort study evaluated whether, among patients with stage IV non-small cell lung cancer (NSCLC) who participated in a pragmatic “alkalization therapy”—defined as a low potential renal acid load diet plus oral sodium bicarbonate and/or potassium/sodium citrate—urinary pH was associated with long-term survival, and whether these associations differed by EGFR/ALK mutation status. Urinary pH was used as a surrogate marker of systemic alkalization. All consecutive patients with stage IV NSCLC who first attended Karasuma Wada Clinic between January 2014, and December 2019 were included (<em>n</em> = 203; EGFR/ALK mutation-negative, <em>n</em> = 100; EGFR/ALK mutation-positive, <em>n</em> = 103). All outpatients received standardized instruction in alkalization therapy. For each patient, a mean urine pH value (excluding the first visit) was calculated. Survival was analyzed using Kaplan–Meier methods with log-rank and Gehan–Breslow–Wilcoxon tests, and Cox proportional hazards regression models incorporating recurrence status and urine pH. Overall, the 5-year survival rate was 49·0 % and was similar by mutation status (EGFR/ALK mutation-positive, 49·9 %; EGFR/ALK mutation-negative, 48·6 %). Among EGFR/ALK mutation-negative patients, postoperative recurrence was associated with a more favorable outcome than de novo stage IV disease at initial diagnosis (5-year survival 65·5 % vs 42·0 %; log-rank <em>p</em> = 0·02). In this subgroup, a mean urine pH ≥7·5 was associated with superior 5-year survival (70·0 % vs 39·3 %; log-rank <em>p</em> = 0·04). Given potential confounding, this shows association—not a causal benefit. Urinary pH may serve as a pragmatic marker of acid–base status, particularly in EGFR/ALK-mutation-negative disease.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102677"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030931","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-stroma contributes to immunotherapeutic resistance in non-small cell lung cancer via SEMA3C-mediated immunosuppressive tumor microenvironment","authors":"Huanyan Zhang ,&nbsp;Hongxin Lin ,&nbsp;Jian Wang ,&nbsp;Di Wu ,&nbsp;Qian Wang ,&nbsp;Jie Mei ,&nbsp;Qing Li ,&nbsp;Yichao Zhu ,&nbsp;Yun Cai","doi":"10.1016/j.tranon.2026.102679","DOIUrl":"10.1016/j.tranon.2026.102679","url":null,"abstract":"<div><h3>Background</h3><div>The tumor-stroma proportion (TSP) was a critical factor influencing clinical outcomes in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms driving TSP-associated aggressiveness and its contribution to immune checkpoint blockade (ICB) resistance remained poorly understood.</div></div><div><h3>Methods</h3><div>Using H&amp;E staining data from the TCGA-NSCLC cohort, patients were stratified into TSP-high and low groups. Transcriptomic profiling and single-cell RNA sequencing (scRNA-seq) were employed to identify the TSP signatures. Functional validation was conducted to investigate the role of SEMA3C in cancer-associated fibroblasts (CAFs) and its influence to tumor cells and T cells.</div></div><div><h3>Results</h3><div>TSP-high status independently predicted worse overall survival (OS) and correlated with ICB resistance. Transcriptomic analysis identified seven TSP-related genes enriched in stromal fibroblasts. Among these signatures, SEMA3C emerged as the key TSP biomarker associated with an immunosuppressive tumor microenvironment (TME) and ICB resistance in NSCLC. Functionally, SEMA3C knockdown in CAFs suppressed their migratory capacity and collagen production. Co-culture experiments demonstrated that compared to SEMA3C-knockdown CAFs, control CAFs significantly enhanced tumor cell migration and invasion while suppressing the activation and proliferation of CD8⁺ T cells. Strikingly, <em>in vivo</em> targeting of SEMA3C inhibited tumor growth.</div></div><div><h3>Conclusion</h3><div>TSP served as an independent prognostic biomarker and predictor of ICB resistance in NSCLC. SEMA3C was identified as a crucial mediator within this axis, promoting tumor malignancy and fostering an immunosuppressive TME characterized by stromal remodeling and excluded anti-tumor immunity. This study established TSP as a clinically relevant stratification tool and revealed stromal-immune crosstalk.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102679"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012560","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":"Improving photodynamic therapy efficacy in bladder cancer using polymer micelle-encapsulated pheophorbide a","authors":"Maxime Labroy ,&nbsp;Stéphane Chabaud ,&nbsp;Maud Durand ,&nbsp;Isabelle Fourquaux ,&nbsp;Stéphane Bolduc ,&nbsp;François Bordeleau ,&nbsp;Laure Gibot","doi":"10.1016/j.tranon.2026.102687","DOIUrl":"10.1016/j.tranon.2026.102687","url":null,"abstract":"<div><h3>Background</h3><div>Photodynamic diagnosis (PDD) is widely used in bladder cancer management, enabling fluorescence-guided detection of lesions through intravesical administration of photosensitizers such as hexaminolevulinate (Cysview®/Hexvix®). Building on this clinical framework, we explored photodynamic therapy (PDT) using pheophorbide <em>a</em> (pheo), a chlorophyll-based photosensitizer, encapsulated in self-assembled poly(ethylene oxide)-block-poly(<em>ε</em>-caprolactone) (PEO₅₀₀₀-PCL₄₀₀₀) micelles.</div></div><div><h3>Results</h3><div><em>In vitro</em> assays were performed on human bladder cancer cell lines, namely the grade 3 invasive T24 and the grade 1 SW780, in both 2D monolayers and 3D spheroid cultures. In 2D, encapsulated pheo showed higher phototoxicity (IC₅₀: 129 nM T24, 156 nM SW780), while free pheo exhibited negligible effects, preventing IC₅₀ determination. Two-photon microscopy confirmed that encapsulation markedly enhanced pheo penetration, especially in T24. SW780 spheroids exhibited tight epithelial features and low permeability, forming characteristic microbladder-like vesicles. PDT reduced viability in both T24 and SW780 3D models, with a significant advantage for encapsulated pheo at day 6 post-treatment in T24 spheroids. Preliminary exploration in human tissue-engineered bladder tumor substitutes demonstrated the feasibility for PDT assessment in complex 3D environments, warranting further study.</div></div><div><h3>Conclusions</h3><div>These findings support polymer nanocarrier-mediated pheo delivery as a promising therapeutic approach and pave the way for integrated diagnostic–therapeutic strategies using existing intravesical platforms.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102687"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133025","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":"WISP1 is the stromal-secreting oncoprotein via paracrine downregulation of NDRG1, KAI1, and Maspin in human bladder cancer cells","authors":"Syue-Ting Chen ,&nbsp;Kang-Shuo Chang ,&nbsp;Chen-Pang Hou ,&nbsp;Wei-Yin Lin ,&nbsp;Shu-Yuan Hsu ,&nbsp;Hsin-Ching Sung ,&nbsp;Tsui-Hsia Feng ,&nbsp;Yu-Hsiang Lin ,&nbsp;Horng-Heng Juang","doi":"10.1016/j.tranon.2026.102680","DOIUrl":"10.1016/j.tranon.2026.102680","url":null,"abstract":"<div><div>WNT1 inducible signaling pathway protein 1 (WISP1) is a connective tissue growth factor that regulates various cellular functions in different tissues but has yet to be examined in the human bladder. Two isoforms of WISP1 (WISP1v1 and WISP1v2) expressed only in bladder fibroblast (HBdSF) and smooth muscle (HBdSMC) cells but not in bladder cancer cells <em>in vitro</em>. TNF-α treatment-induced IL-6, CXCL5, and SDF-1 expressions in bladder stroma cells. TNF-α-induced IL-6 depends on the WISP1, and the TNF-α-activation was suppressed under CAPE treatment. WISP1-knockdown inhibited the proliferation and contraction of HBdSMC and HBdSF cells, while the conditioned media from either ectopic WISP1v1- or WISP1v2-overexpressed 293T cells stimulated both the proliferation of HBdSF and HBdSMC cells. The supernatant of WISP1-knockdown in HBdSMC cells reduced the migration of bladder carcinoma T24 cells. WISP1v1, but not WISP1v2, enhanced cell growth, migration, and invasion in bladder cancer cells via downregulating NDRG1, KAI1, and Maspin expressions. Silico's analysis confirmed that WISP1 is a potential oncogene in human bladder cancer. Results suggest that WISP1, a stroma-specific secreted protein, modulates the behavior of bladder stroma cells via autocrine signaling. WISP1 induces tumor growth of bladder carcinoma cells in an isoform-dependent manner via paracrine signaling, indicating that WISP1 may behave as a mediator linking diseases of the human bladder.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102680"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079445","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":"POSTN⁺ cancer-associated fibroblast–CCL3⁺ macrophage crosstalk defines the immune-excluded tumor microenvironment in clear cell renal cell carcinoma","authors":"Yingjian Wang ,&nbsp;Bingtong Yue ,&nbsp;Hongqiang Ni ,&nbsp;Jinchun Chen ,&nbsp;Run Shi ,&nbsp;Zhe Wang ,&nbsp;Xinglai Dai ,&nbsp;Maolin Sheng","doi":"10.1016/j.tranon.2026.102682","DOIUrl":"10.1016/j.tranon.2026.102682","url":null,"abstract":"<div><h3>Background</h3><div>Clear cell renal cell carcinoma (ccRCC) frequently exhibits an immune-excluded tumor microenvironment (TME) that limits the efficacy of immune checkpoint blockade (ICB). However, the stromal–immune interactions responsible for this exclusion remain poorly understood.</div></div><div><h3>Methods</h3><div>We integrated eight single-cell RNA sequencing datasets, two spatial transcriptomic datasets, and bulk transcriptomic cohorts to construct a comprehensive ccRCC TME atlas. Fibroblast subsets were characterized using clustering, trajectory, transcription-factor regulon, and gene-network analyses. Stromal–immune signaling was assessed using CellChat and NicheNet, and spatial colocalization patterns were validated by SpaGene analysis. Prognostic and therapeutic relevance were evaluated in TCGA-KIRC and ICB-treated cohorts.</div></div><div><h3>Results</h3><div>Seven fibroblast subtypes were identified, among which periostin (POSTN)–positive cancer-associated fibroblasts (CAFs) were selectively enriched in tumors and exhibited strong activation of TGF-β, PI3K–AKT, and extracellular-matrix pathways. Trajectory and regulon inference revealed GATA6 as a key transcriptional regulator driving fibroblast differentiation toward this ECM-remodeling phenotype. Spatial analyses demonstrated that POSTN⁺ CAFs colocalized with CCL3-positive macrophages at the invasive front, forming a hypoxic, fibrotic niche that excluded CD8⁺ T cells. Ligand–receptor mapping identified reciprocal TGF-β, SPP1, and IL-6 signaling that reinforced fibro-myeloid activation. Activation of the POSTN⁺ CAF–CCL3⁺ macrophage axis correlated with poor survival and reduced response to ICB therapy.</div></div><div><h3>Conclusions</h3><div>This study defines a spatially organized stromal–immune signaling axis that drives immune exclusion and immunotherapy resistance in ccRCC. Targeting the POSTN⁺ CAF–CCL3⁺ macrophage interaction offers a promising strategy to remodel the fibrotic barrier and restore antitumor immunity.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102682"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039060","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":"Utilization of machine learning algorithms for the identification of the RLN associated prognostic model and feature biomarkers of RLN-related subtypes in breast cancer","authors":"Yi Du ,&nbsp;Quan Yuan ,&nbsp;Hao Yu ,&nbsp;Rongjie Ye ,&nbsp;Huan Lin ,&nbsp;Ge Yu ,&nbsp;Ming Niu ,&nbsp;Huilei Qiu","doi":"10.1016/j.tranon.2026.102684","DOIUrl":"10.1016/j.tranon.2026.102684","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) is the most common malignancy afflicting women worldwide, yet the role of relaxin-related genes (RLN) in BC progression remains unclear. This study aims to elucidate the relationship between RLN and BC outcomes through immune microenvironment and metabolic pathway analysis.</div></div><div><h3>Methods</h3><div>Gene expression and clinical data were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Relaxin-related genes were identified using KEGG and Genecard databases. A prognostic model, the RLN Associated Prognostic Model (TRAPM), was established using 101 combinations of 10 machine learning algorithms and validated at the single-cell level. Multi-omics analysis, including the IMvigor210 cohort, was performed to assess TRAPM’s applicability in immunotherapy and drug selection.</div></div><div><h3>Results</h3><div>TRAPM, comprising nine prognostic genes (MMP1, RXFP1, PRKCZ, JUN, NFKBIA, GNAI2, NOS2, MMP9, and MMP13), showed significant associations with immune and metabolic profiles. Using TRAPM, a novel BC subtype RC3 and its key marker genes (MTHFD1L, CAVIN4, MMP1, ADGRG6, B3GNT5, SMYD2, and TFRC) were identified. Experimental validation through RT-qPCR and Western Blot confirmed the role of these markers in six BRCA cell lines.</div></div><div><h3>Conclusions</h3><div>The identification of TRAPM and the RC3 subtype enhances our understanding of BC heterogeneity and highlights potential therapeutic targets. This study provides a foundation for personalized treatment strategies by clarifying the biological significance and clinical relevance of the RC3 subtype.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102684"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039061","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 cancer stem cells as the most aggressive and tumor-initiating cells","authors":"Maryam Sadri ,&nbsp;Zahra Shafaghat ,&nbsp;Mona Roozbehani ,&nbsp;Maryam Dorfaki ,&nbsp;Fatemeh Kheiri ,&nbsp;Sahel Heidari ,&nbsp;Ali Mahmoudi ,&nbsp;Fatemeh Faraji","doi":"10.1016/j.tranon.2026.102669","DOIUrl":"10.1016/j.tranon.2026.102669","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are a small subpopulation of tumor cells characterized by their self-renewal capacity and the ability to differentiate into different cell types. These partially differentiated cells exhibit properties of both stem cells and cancer cells. CSCs drive tumor initiation and progression by generating additional stem cells through self-renewal and differentiation into heterogeneous populations of tumor cell. They are among the most aggressive tumor cells that contribute to the development of key features of malignancy such as increased proliferation, metastasis, tumor growth, multidrug resistance (MDR), and resistance to radiotherapy and chemotherapy. CSCs are also associated with relapse and minimal residual disease, highlighting their critical role in cancer persistence. Therefore, targeting CSCs is essential to achieve complete tumor eradication. Available evidence suggests that combination therapies that integrate immunotherapy with cytotoxic therapies to concurrently eliminate CSCs and non-CSCs offer a promising approach to completely eradicate cancer. This review summarizes the current strategies employed to target CSCs and improve cancer treatment outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102669"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079446","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":"Androgen receptor may promote tumor progression via TTF-1/EGFR pathway in metastatic nasopharyngeal carcinoma","authors":"Chiao-Yun Lin ,&nbsp;Chen-Yang Huang ,&nbsp;Kar-Wai Lui,&nbsp;Yin-Kai Chao,&nbsp;Chun-Nan Yeh,&nbsp;Li-Yu Lee,&nbsp;Yenlin Huang,&nbsp;Zhangung Yang,&nbsp;Chia-Hsun Hsieh,&nbsp;Hsien-Chi Fan,&nbsp;An-Chi Lin,&nbsp;Kai-Ping Chang,&nbsp;Chien-Yu Lin,&nbsp;Hung-Ming Wang,&nbsp;Mei Chao,&nbsp;Yu-Sun Chang,&nbsp;Hsin-Pai Li,&nbsp;Cheng-Lung Hsu","doi":"10.1016/j.tranon.2026.102670","DOIUrl":"10.1016/j.tranon.2026.102670","url":null,"abstract":"<div><div>Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia, including Taiwan. It exhibits higher morbidity as well as mortality in males than in females. However, the role of the androgen receptor (AR) in NPC remains unclear. In this study, AR expression was detected in most NPC cell lines and patient-derived xenografts. Treatment with enzalutamide, an antiandrogen, substantially inhibited patient-derived xenografts growth and demonstrated additive antitumor effects when combined with chemotherapy in AR-positive models. Additionally, transcriptome analysis following enzalutamide treatment revealed activation of hypoxia-inducible factor-1, steroid hormone, and AR pathways, alongside suppression of interferon and tumor necrosis factor pathways. Protein analysis further supported these transcriptomic changes. In AR-overexpressing NPC-B13 cells, AR appeared to regulate thyroid transcription factor-1 (TTF-1, encoded by <em>NKX2–1</em> gene) and its downstream target epidermal growth factor receptor (EGFR), thereby promoting cancer cell proliferation. Furthermore, chromatin immunoprecipitation suggested that AR may directly bind to the <em>NKX2–1</em> promoter to upregulate its mRNA expression. Under AR overexpression, Epstein-Barr virus (EBV) remained in a latent state, accompanied by suppression of lytic gene expression. Additionally, Epstein–Barr nuclear antigen-1 enhanced AR transactivation in a dose-dependent manner in NPC cell line reporter assays. Among 96 metastatic NPC tumor samples, AR expression was observed in 35 cases (36.5%), predominantly in males (33/83, 39.8%). AR expression correlated with poorer overall survival, with statistical significance noted in the full cohort and particularly in male patients. This study suggests that AR may promote metastatic NPC progression via the TTF-1/EGFR signaling pathway and interact with EBV to influence disease behavior, especially in males.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"65 ","pages":"Article 102670"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114290","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 derived adiponectin induces immunosuppressive macrophages in upper tract urothelial carcinoma","authors":"Cheng-Huang Shen ,&nbsp;PiChe Chen ,&nbsp;Chia-Bin Chang ,&nbsp;Chih-Chia Chang ,&nbsp;Meilin Wang ,&nbsp;Lien-Ping Chou ,&nbsp;Ya-Yan Lai ,&nbsp;Ming-Yang Lee ,&nbsp;Shu-Fen Wu","doi":"10.1016/j.tranon.2025.102599","DOIUrl":"10.1016/j.tranon.2025.102599","url":null,"abstract":"<div><div>Upper tract urothelial carcinoma (UTUC) is a rare urologic cancer that is more aggressive and has a poorer survival rate compared to bladder cancer. Previously, we linked the UTUC derived factors with tumor-infiltrating immune cells. Macrophages are considered the most abundant immune cell population within tumors and serve as key regulators of the tumor microenvironment. This study aimed to investigate their role in modulating immunosuppression in UTUC tumors. Our results indicated that UTUC patients had higher proportion of M2-type macrophages in the periphery, and that tumor-infiltrating M2 macrophages were inversely correlated with tumor-infiltrating T lymphocytes within UTUC tumors. The supernatants from UTUC tumor tissue, as well as the predominant factor adiponectin, caused upregulation of arginase-1 and CD206 expression in THP-1 differentiated macrophages. Furthermore, macrophages treated with supernatants from UTUC tumor tissue or adiponectin alone inhibited CD4 T cell and CD8 T cell proliferation, along with reduction of effective cytokines produced by T cells. These results suggest that macrophages modulated by adiponectin are associated with T cell suppression in the UTUC tumor microenvironment, highlighting a potential therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"64 ","pages":"Article 102599"},"PeriodicalIF":5.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913096","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}