International Journal of Cancer最新文献

{"title":"The critical role of discoidin domain receptors in the regulation of anti-tumor immune responses.","authors":"Sixin Jiang, Yan Qiu, Qiuhao Wang, Xiangfei Liu, Yidi Zhang, Haifen Feng, Qianming Chen, Yuchen Jiang, Xiaobo Luo","doi":"10.1002/ijc.70398","DOIUrl":"10.1002/ijc.70398","url":null,"abstract":"<p><p>Discoidin domain receptors (DDRs) are nonintegrin collagen receptors which could be activated by various collagens. Overexpressed in numerous cancers, DDRs participate in tumorigenesis, tumor growth, dissemination, and metastasis. Immune checkpoint inhibitors (ICIs) have demonstrated low response rates in tumors such as head and neck cancer and pancreatic cancer, possibly due to the insufficient presence of effector T cells and the abundant collagen fibers in the tumor microenvironment. Recently, several studies indicate that DDRs account for ICIs resistance. For instance, DDR1 can prevent the anti-tumor immune responses via mediating the rearrangement of collagen fibers, increasing the secretion of interleukin-18 (IL-18) as well as facilitating the formation of neutrophil extracellular traps (NETs). DDR2 may participate in the establishment of immunosuppressive tumor microenvironment by recruiting myeloid-derived suppressor cells (MDSCs) and promoting the M2 polarization of macrophages. Notably, the interaction between collagens and immune cells also acts as a pivotal role in mediating tumor immune escape. Targeting DDRs and upstream regulators including collagen has been reported to significantly restore the antitumor immunity or inhibit tumor development, such as utilizing DDR1 inhibitors via AI screening from FDA-approved therapeutics or natural products, and strategies for collagen synthesis inhibition or collagen degradation. However, the above approaches are largely limited to preclinical studies and still warrant further validation in clinical trials. Based on the current evidences, DDRs serve as promising targets for improving the efficacy of ICIs against cancers; more studies are anticipated to reveal unclarified mechanisms of DDRs in regulating anti-tumor immunity.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3080-3090"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147300438","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":"Molecular-clinical characteristics and treatment outcomes in 163 metastatic colorectal neuroendocrine carcinomas with a comparison to colorectal adenocarcinomas.","authors":"Siren Morken, Seppo W Langer, Geir Olav Hjortland, Anna Sundlöv, Eva Hofsli, Morten Ladekarl, Elizaveta Tabaksblat, Lene Weber Vestermark, Johanna Svensson, Ulrich Knigge, Luís Nunes, Bengt Glimelius, Per Pfeiffer, Kristine Aasebø, Jörg Assmus, Erik Vassella, Inger Marie Bowitz Lothe, Anne Couvelard, Aurel Perren, Stian Knappskog, Halfdan Sorbye","doi":"10.1002/ijc.70367","DOIUrl":"10.1002/ijc.70367","url":null,"abstract":"<p><p>There is limited data regarding the rare and aggressive colorectal neuroendocrine carcinoma (CR-NEC). In this large prospective study, molecular-clinical characteristics and treatment outcomes following palliative chemotherapy are reported for 163 metastatic CR-NEC patients, with a comparison to a population-based prospective cohort of 263 metastatic colorectal adenocarcinoma (CR-AC) patients. Eighty-three percent of CR-NEC received first-line platinum-etoposide, while 98% of CR-AC patients received first-line fluorouracil-based chemotherapy. Disease control rate across all first-line regimens in CR-NEC and CR-AC was 43% vs. 74%, immediate progressive disease 46% vs. 15%, progression-free survival 2.4 months (m) (95% CI 2.1-3.3) vs. 7.7 m (95% CI 6.9-8.5), and overall survival 6.7 m (95% CI 5.6-8.8) vs. 16.8 m (95% CI 13.7-20.3), all, p < .001. CR-NEC more often had synchronous metastases, worse performance status, and symptom burden at treatment initiation than CR-AC (all, p < .001). Two-year survival was 9% vs. 37% in CR-NEC and CR-AC (p < .001). BRAF mutations were frequent in CR-NEC and CR-AC (26% vs. 20%, p = .153) and associated with shorter OS in CR-NEC and CR-AC (p = .025 and p = .003). KRAS mutations were less frequent in CR-NEC than CR-AC (34% vs. 45%, p = .041), but only associated with shorter OS in rectal NEC (p = .04). The frequencies of APC and TP53 mutations were similar between the cohorts and did not impact survival. Metastatic CR-NEC and CR-AC are clinically distinct, with NEC demonstrating more aggressive features, limited treatment effect, and worse prognosis. Although they share important driver mutations, the underlying reason for their marked clinical differences remains unclear.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3217-3231"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low T3 syndrome in children with aggressive mature B-cell non-Hodgkin lymphoma.","authors":"Da Li, Nan Li, Shuang Huang, Meng Zhang, Ling Jin, Jing Yang, Wanyu Dang, Wenli Zhao, Hongmei Huang, Jie Yan, Yanlong Duan","doi":"10.1002/ijc.70335","DOIUrl":"10.1002/ijc.70335","url":null,"abstract":"<p><p>Low triiodothyronine (T3) syndrome, also known as non-thyroidal illness syndrome (NTIS), was one of the common endocrinopathies in critical illness. The potential impacts of low T3 syndrome on survival, endocrine function, and nutritional status of patients with aggressive mature B-cell non-Hodgkin lymphoma (NHL) needed to be explored. We enrolled 225 patients. T3 levels were captured when starting chemotherapy, finishing chemotherapy, and at the first follow-up visit from 6 months after chemotherapy. Latest ultrasound results were recorded. Kaplan-Meier curves were used to compare overall survival (OS) or progression-free survival (PFS). We performed Cox's proportional hazards regression model to analyze prognostic factors of OS and PFS. Ultrasound abnormality and weight gain were tested with the χ² test. The percentage of patients with low T3 syndrome decreased from 55.1% (124 out of 225) to 2.0% (4 out of 201), then further dropped down to 0 (0 out of 173). With a median follow-up of 32.9 months, low T3 syndrome was identified as a statistically significant factor affecting both OS (p = .047; hazard ratio [HR] = 8.18, 95% CI: 1.03-64.97) and PFS (p = .049; HR = 4.64, 95% CI: 1.01-21.31) in multivariate analysis. No significant effects of low T3 syndrome on abnormal thyroid ultrasound results and weight gain were found. In conclusion, low T3 syndrome has a high incidence in pediatric patients with aggressive mature B-cell NHL, and low T3 syndrome has a significant impact on long-term survival. It appears transient and could not contribute to impaired thyroid function.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3112-3120"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987354","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":"TP53 mutation is associated with improved disease control in patients with advanced RAS wild-type colorectal adenocarcinoma treated with cetuximab and pembrolizumab.","authors":"Christos Fountzilas, Spencer Rosario, Agnieszka K Witkiewicz, Henry G Withers, David L Bajor, Sarbajit Mukherjee, Joel Saltzman, Orla Maguire, Hans Minderman, Sarah Chatley, Mary Lynn Tarquini, Amy Whitworth, Jennifer Jurcevic, Hua-Hsin Hsiao, Erik S Knudsen, Jason B Muhitch, Scott I Abrams, Pawel Kalinski, Brahm H Segal, Andrei Bakin, Guangwei Yuan, Chong Wang, Kristopher Attwood, Renuka Iyer, Patrick M Boland","doi":"10.1002/ijc.70434","DOIUrl":"10.1002/ijc.70434","url":null,"abstract":"<p><p>Immunotherapy with checkpoint inhibitors targeting the PD1/PD-L1 and CTLA4 pathways has limited activity in patients with microsatellite stable (MSS) colorectal adenocarcinoma (CRC). In a prior study, the combination of cetuximab and pembrolizumab failed to improve outcomes for patients with advanced RAS wild-type (RAS^wt) CRC. In this post hoc secondary analysis, we show that the cetuximab and pembrolizumab-treated patients with TP53 mutant (p53^mt) tumors had significantly higher progression-free survival (PFS) and a decrease in tumor burden compared to patients with TP53 wild-type (p53^wt) tumors but no difference in overall survival compared to patients with p53^wt tumors. The gene set enrichment analysis showed a uniform upregulation of multiple metabolic and immune gene sets, including NK-mediated immunity and IL-12 pathway, while the IL6 pathway was downregulated. There were no overlapping transcriptional alterations between the p53^mt and p53^wt groups with treatment that remain constant despite the therapeutic intervention. Functional overlap with treatment in both groups in the proliferative, immune, and metabolic pathways were identified. In the baseline tumor samples, the number of PD-L1⁺ tumor cells was significantly higher in p53^mt tumors while the number of OX40^-/AE1_AE3^-/PD-L1^- non-tumor cells, positive for either LAG3, CTLA4 or TIM3, was significantly higher in p53^wt tumors. In conclusion, TP53 status was prognostic of improved PFS with cetuximab plus pembrolizumab in RAS^wt CRC. Future studies evaluating immune-oncology agents in patients with MSS, RAS^wt CRC should include TP53 as an integrated biomarker and evaluate its performance as a positive predictive biomarker (ClinicalTrials.gov NCT02713373).</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3300-3311"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147371874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward a validated European instrument to measure the socioeconomic impact of cancer.","authors":"Jasper Ubels, Julie M Vancoppenolle, Josephine Tetteh, Wim H van Harten, Valesca P Retèl, Michael Schlander, Nora Franzen","doi":"10.1002/ijc.70364","DOIUrl":"10.1002/ijc.70364","url":null,"abstract":"<p><p>A cancer diagnosis can impose a financial burden on patients and their families, defined as socio-economic impact (SEI) within a framework of the Organization of European Cancer Institutes (OECI). The Socio-Economic Consequences of Cancer (SEC) study assessed SEI in 25 European countries using the Canadian Financial Index of Toxicity (FIT) instrument, showing substantial variation and supporting the need for a validated Europe-specific instrument. We examined the FIT instrument's validity and reliability in a secondary analysis of the SEC study, exploring whether the SEI framework supported its validation. Factor analyses were performed on the largest subgroup sharing cancer type, language, and country. The aim was to test whether the Canadian model could be replicated or a SEI-based model fit better. Reliability and construct validity were analyzed, followed by configural invariance and Differential Item Functioning (DIF) analysis for cross-country comparability. We used data from Bulgaria, France, Germany, the Netherlands, Norway, and Spain. The original FIT-instrument failed to replicate in the Spanish sample, leading to an SEI-based model with better fit (CFI = 0.975, RMSEA (90% CI) = 0.104 (0-0.278), χ² = 18, p = .60). The instrument was reliable. Construct validity was partly confirmed. Configural invariance testing suggested that the SEI-based model's factor structure fits better in Europe, while DIF was identified, implying that direct score comparisons across countries should be done with care. In conclusion, the original FIT-instrument could not be fully validated in Europe whereas the SEI-framework improved score interpretation, supporting its use in developing a validated instrument tailored to the European context.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3288-3299"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cumulative exposure to tacrolimus is associated with increased risk of malignancy for solid organ transplant recipients.","authors":"Sergio A Acuna, Xun Zhao, Maggie Jones-Carr, Graham Smith, Kyla Naylor, Bima J Hasjim, Shiyi Chen, An-Wen Chan, Nancy Baxter, S Joseph Kim, Mamatha Bhat","doi":"10.1002/ijc.70343","DOIUrl":"10.1002/ijc.70343","url":null,"abstract":"<p><p>Solid organ transplant recipients (SOTR) face elevated cancer risk due to prolonged immunosuppression. While higher tacrolimus exposure has been linked to de novo malignancies, the dose-response relationship remains unclear, prompting the need for population-level, longitudinal investigations. To quantify the exposure-response relationship between tacrolimus trough level and post-transplant malignancy risk, we used a population-based cohort study using linked administrative healthcare data from Ontario, Canada. All transplant recipients from January 1, 2008 to March 1, 2020 with ≥2 serum tacrolimus levels in the first year post-transplant were included. Cumulative exposure to tacrolimus was treated as a (1) continuous variable, (2) by quartiles of exposure within the first year and (3) as time-varying exposure beyond the first year; incidence of de novo malignancy was investigated using cause-specific and subdistribution Cox regression models. Among the 5178 SOTRs, a total of 318 de novo malignancies (6.1%) and 332 deaths (6.4%) occurred. For every 20% increase in the cumulative tacrolimus trough level in the first year, a heightened risk of malignancy was observed (HR = 1.09, 95% CI: 1.02-1.17). For each 20% increase in cumulative tacrolimus trough level after 1 year, the risk of malignancy increased (HR = 1.08 [95% CI: 1.01-1.15]). Patients in the highest quartile of cumulative exposure (median 9-10 ng/mL) had a 47% greater risk of malignancy compared to those in the lowest quartile (median 5-6 ng/mL; HR = 1.47 [95% CI: 1.03-2.11]). These findings highlight the importance of carefully titrating tacrolimus and avoiding unnecessary prolonged high exposure, particularly during the critical first year post-transplant.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3152-3160"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single versus repeated intravenous oncolytic reovirus infusions: Implications for immune modulation and rationalised scheduling of therapy in hepatocellular carcinoma.","authors":"Karen J Scott, Emma J West, Rebecca J Brownlie, Fay Ismail, Christy Ralph, Thomas Heineman, Matt Coffey, Alan A Melcher, Alison Taylor, Salvatore Papa, Adel Samson","doi":"10.1002/ijc.70386","DOIUrl":"10.1002/ijc.70386","url":null,"abstract":"<p><p>Scheduling of oncolytic virus (OV) therapy has never been correlated with immunological/clinical response. In hepatocellular carcinoma (HCC) patients, where background liver is frequently chronically injured, repeated dosing may have deleterious implications, resulting in off-target immune-mediated damage, thereby tipping the balance between favourable clinical response and hepatotoxicity. Elucidation of the optimum dosing regime is paramount to ensure therapy, whilst limiting damage to background liver. We expand upon our experience in neoadjuvant OV therapy to compare immunological responses from single versus repeated doses of reovirus in cancer patients. The impact of OV on HCC outcomes was examined in vivo following a high-fat diet or induced liver fibrosis in the context of abnormal background liver. Furthermore, we assess the potential immune-mediated toxicity of single versus multiple virus infusions in combination with PD-1/PD-L1 blockade. Data indicate that a single dose of reovirus is equivalent or superior to repeated doses in achieving: (a) induction of an inflammatory cytokine/chemokine response; (b) peripheral blood immune cell activation; (c) migration of activated CD8+ CTLs. Repeated doses on consecutive days do not improve the amplitude of the immune response following virus infusion. Furthermore, without improving therapeutic efficacy, repeated viral dosing leads to an unwanted influx of activated T-cells into background liver, alongside elevated liver enzymes associated with aberrant liver function. A single dose of reovirus is as effective as multiple doses when combined with anti-PD-L1 therapy in limiting tumour growth and extending survival in vivo, whilst simultaneously avoiding undesirable toxicities in background liver, in the context of HCC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3252-3267"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of first-line immunochemotherapy across KRAS mutation subtypes in advanced lung adenocarcinoma.","authors":"Hongping Jin, Honglei Huang, Yiqing Wu, Yidan Zhang, Jianlin Xu, Tengfei Liu, Hua Zhong, Qian Miao, Runbo Zhong","doi":"10.1002/ijc.70362","DOIUrl":"10.1002/ijc.70362","url":null,"abstract":"<p><p>The impact of KRAS mutation subtypes on treatment response to first-line immunochemotherapy in advanced lung adenocarcinoma (LUAD) remains uncertain. This study evaluated treatment efficacy across KRAS subtypes and examined the role of programmed death-ligand 1 (PD-L1) expression and co-mutations. We retrospectively analyzed 335 patients with advanced KRAS-mutant LUAD treated with first-line immunochemotherapy between 2018 and 2022 at two centers. Patients were categorized into G12A (n = 36), G12C (n = 116), G12D (n = 62), G12V (n = 56), and other subtypes (n = 65). PD-L1 tumor proportion score (TPS) was stratified as <1%, 1-49%, or ≥50%. Endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Median PFS in the overall cohort was 8.6 months, with an ORR of 34.0% and a DCR of 87.8%. Median PFS did not differ significantly among KRAS subtypes (p = .617), nor within PD-L1 TPS groups: <1% (p = .740), 1-49% (p = .652), and ≥50% (p = .481). In the major subtypes (G12A, G12C, G12D, and G12V), PD-L1 expression showed no significant association with PFS. STK11 co-mutations were enriched in G12C, G12V, and other subtypes (p = .004) and correlated with shorter PFS (p = .006). In conclusion, first-line immunochemotherapy yields comparable efficacy across KRAS subtypes, independent of PD-L1 expression. Within the major subgroups (G12A, G12C, G12D, and G12V), PD-L1 levels were not predictive of PFS. STK11 co-mutations were enriched in G12C, G12V, and other subtypes and were associated with shorter PFS.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3187-3196"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111627","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 phase II trial of naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in second or later complete remission.","authors":"Brian H Kushner, Shakeel Modak, Charlie White, Ellen M Basu, Stephen S Roberts, Audrey Mauguen, Nai-Kong V Cheung","doi":"10.1002/ijc.70374","DOIUrl":"10.1002/ijc.70374","url":null,"abstract":"<p><p>Relapse of high-risk neuroblastoma (HR-NB) poses a challenge to cure. Increasing numbers of HR-NB patients achieve post-relapse complete remission (CR) because close monitoring can detect localized disease and novel effective salvage therapies have emerged. We report outcome with immunotherapy using the anti-G_D2 monoclonal antibody (mAb) naxitamab and granulocyte-macrophage colony-stimulating factor (GM-CSF) for consolidation of second or later CR in a phase II trial (Clinicaltrials.gov NCT01757626). Cycles included GM-CSF 250 μg/m²/day on days -4-to-0 and increased to 500 μg/m²/day on days +1-to-5, and 3 doses of naxitamab infused (30-to-90 min) on days +1/+3/+5, 3 mg/kg/infusion (9 mg/kg/cycle, i.e., ~270 mg/m²/cycle). Cycles were monthly ×5. Clinical factors assessed regarding prognosis were: MYCN amplification; localized versus widespread prior relapse; 1 versus ≥2 prior relapse(s); previous treatment with anti-G_D2 mAb; and time from diagnosis to 1st relapse. Sixty patients were enrolled after 1 (n = 42) or ≥2 (n = 18) prior relapse(s); 27 (45%) had MYCN amplification. Progression-free survival (PFS) rates at 2/5 years were 55%/50%. Prior treatment with naxitamab and prior widespread relapse had significant negative impacts on PFS. Post-protocol patients in CR routinely received an investigational anti-NB vaccine. Two other patients, both with 1 prior relapse, took DFMO. Naxitamb+GM-CSF is a good option to consolidate post-relapse CR of HR-NB. The encouraging long-term outcome cannot be attributed solely to naxitamab+GM-CSF given post-protocol therapies.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3232-3240"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155337","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":"Antiviral regulator TRIM25 as a prognostic marker of better survival in Merkel cell carcinoma: Association with MCPyV status.","authors":"Klaus W Fagerstedt, Sami Kilpinen, Johanna Arola, Benjamin Z Sundqvist, Tom Böhling, Leif C Andersson, Harri Sihto","doi":"10.1002/ijc.70384","DOIUrl":"10.1002/ijc.70384","url":null,"abstract":"<p><p>Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer, most often driven by integration of Merkel cell polyomavirus (MCPyV). While anti-PD-1/PD-L1 therapies have improved outcomes, reliable prognostic biomarkers remain limited. Tripartite motif-containing protein 25 (TRIM25), a critical activator of innate immunity, was evaluated here for its clinical and biological relevance in MCC. We analysed TRIM25 mRNA and protein expression in 102 MCC cases and 9 MCC cell lines, respectively, and assessed associations with MCPyV status, clinicopathological characteristics and patient survival. Differential gene expression analysis was performed to identify pathways associated with TRIM25 expression in both low and high TRIM25-expressing tumour groups. High TRIM25 expression was significantly associated with MCPyV positivity in both patient tumours (p = .004) and cell lines (p = .016), and TRIM25 and MCPyV mRNA levels correlated positively in tumours (r = 0.264, p = .013). Patients with low TRIM25 expression had a significantly poorer 5-year disease-specific survival than those with high expression (53% vs. 78%, p = .013). Notably, Cox multivariate analysis confirmed that TRIM25 serves as an independent prognostic marker, irrespective of MCPyV status. Pathway analysis revealed that low TRIM25 expression was linked to antigen presentation pathways, while high TRIM25 expression was associated with cell cycle regulation. Our findings suggest that TRIM25 serves as a valuable prognostic biomarker in MCC. Additionally, TRIM25 may play a pathogenic role in MCPyV-positive tumours, warranting further investigation to elucidate its mechanistic involvement in MCC tumourigenesis.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"3268-3278"},"PeriodicalIF":4.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}