Journal of the National Cancer Center最新文献

{"title":"Efficacy and safety of oral vinorelbine with concurrent radiotherapy in unresectable stage III non-small cell lung cancer following neoadjuvant chemoimmunotherapy: a single-arm, phase 2 trial","authors":"Xinrong Lian ,&nbsp;Gulidanna Shayan ,&nbsp;Shijie Yang,&nbsp;Wenyang Liu,&nbsp;Tao Zhang,&nbsp;Jima Lv,&nbsp;Wenqing Wang,&nbsp;Jianyang Wang,&nbsp;Xin Wang,&nbsp;Zefen Xiao,&nbsp;Zongmei Zhou,&nbsp;Nan Bi,&nbsp;Lei Deng","doi":"10.1016/j.jncc.2025.06.004","DOIUrl":"10.1016/j.jncc.2025.06.004","url":null,"abstract":"<div><h3>Background</h3><div>Individuals with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) who receive complete concurrent chemoradiotherapy (cCRT) can benefit from long-term survival. Although neoadjuvant chemoimmunotherapy (NACIT) have achieved breakthroughs in treating unresectable stage Ⅲ NSCLC, patients who have received induction chemoimmunotherapy are considered poor candidates for cCRT due to concerns about tolerability. Oral vinorelbine chemotherapy is widely used in clinical settings because of its safety, even for frail patients. The objective of this trial was to assess the efficacy and safety of oral vinorelbine plus concurrent radiotherapy (RT) for individuals with unresectable stage Ⅲ NSCLC following NACIT who were not candidates for concurrent intravenous chemotherapy.</div></div><div><h3>Methods</h3><div>This was a single-arm, phase 2 trial. The primary endpoint was the objective response rate (ORR), while the secondary endpoints consisted of the disease control rate (DCR), safety, overall survival (OS), as well as progression-free survival (PFS).</div></div><div><h3>Results</h3><div>Between March 10, 2023 and April 24, 2025, 46 individuals with unresectable stage Ⅲ NSCLC were administered oral vinorelbine plus thoracic RT. Patients were treated with oral vinorelbine (60 mg/m² once a week for 2 weeks as induction therapy before thoracic RT) and 30 mg/m² per week with concurrent RT (59.4–60.2 Gy) over 5.5 weeks. The median age of the patients was 62.5 years, with 42 being male (91.3 %). The ORR was 52.1 % (95 % confidence interval [CI], 35.1 %–65.9 %), with 24 partial responders. A 95.7 % DCR (85.5 %–98.8 %) was observed, and 20 patients had stable disease. The median follow-up was 22.5 months; the median PFS was 18.0 months and the median OS was not reached. The most commonly observed adverse events (AEs) included leukopenia (grade 1, 26.1 %), anemia (grade 1, 17.4 %), neutropenia (grade 1, 10.9 %), acute esophagitis (grade 2, 17.4 %), and treatment-related pneumonitis (grade 1–2, 60.9 %). No grade 3 or 4 treatment-related AEs were recorded.</div></div><div><h3>Conclusion</h3><div>In individuals with unresectable stage Ⅲ NSCLC who had received NACIT and were not candidates for concurrent intravenous chemotherapy with RT, the oral vinorelbine plus concurrent RT demonstrated promising antitumor efficacy with acceptable toxicity profiles.</div></div><div><h3>Trial registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT06540950).</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 6","pages":"Pages 593-599"},"PeriodicalIF":9.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BTEX chrono-metabolism and leukemogenic effects of night shift work in workers of gasoline stations: the EXPOSOWORK prospective panel study in Bulgaria","authors":"Behzad Heibati ,&nbsp;Georgia Soursou ,&nbsp;Samuel Abimbola ,&nbsp;Pantelis Charisiadis ,&nbsp;Lygia Eleftheriou ,&nbsp;Leon A.M. Berge ,&nbsp;Jo S. Stenehjem ,&nbsp;Konstantinos C. Makris","doi":"10.1016/j.jncc.2025.01.006","DOIUrl":"10.1016/j.jncc.2025.01.006","url":null,"abstract":"<div><h3>Background</h3><div>Exposures to benzene, toluene, ethylbenzene and xylenes (BTEX) have been associated with impairment of the hematopoietic system, often leading to leukemogenesis. A prospective panel study: i) characterized the effect of night shift work (NSW) (12-hr night shift vs. 12-hr day shift) on urinary BTEX and metabolites in gasoline station workers in Plovdiv, Bulgaria, ii) evaluated the NSW effect on chrono-based BTEX genotoxic effects (as measured by 8-OHdG, a nonspecific biomarker of genotoxicity) including the influence of the downstream urinary metabolome.</div></div><div><h3>Methods</h3><div>During a week's working period, workers (n=71) followed both day shift and night shift work schedules (12-h long each shift) collecting four urine samples per worker (pre and end of shift). Airborne BTEX exposures were evaluated over 12-h shift periods using wearable passive samplers. Urinary BTEX and the metabolome were measured using mass spectrometry. 8-OHdG was measured using an ELISA immunoassay. Associations were examined using mixed-effect regression models and corrected for false-discovery rates of 0.05.</div></div><div><h3>Results</h3><div>Median personal airborne benzene levels were 3.05 (IQR: 2.89), and 2.92 (IQR: 1.86) μg/m³ for day and night work shifts, respectively, suggestive of a low-level BTEX study. Results supported a consistent trend of lower urinary BTEX levels in NSW than those observed in day shift, after adjusting for airborne BTEX and confounders. Metabolomic signatures revealed a few significant metabolites associated with NSW or 8-OHdG with 4-hydroxybenzeneacetic acid (level I) being associated with both NSW and 8-OHdG. The biological pathway with high metabolic pathway impact were glycine, serine and threonine metabolism.</div></div><div><h3>Conclusion</h3><div>Larger NSW studies with longer and more frequent follow-up times are warranted to better delineate the possible influence of NSW chrono-modulated working activities in leukemogenic processes.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 537-546"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the landscape of targeting mitochondrial functions and behaviors to overcome cancer chemoresistance","authors":"Haoyan Zhang ,&nbsp;Sicheng Wang ,&nbsp;Peng Wu ,&nbsp;Zanmin Hu ,&nbsp;Yani Chen ,&nbsp;Yupeng Guan ,&nbsp;Jun Pang","doi":"10.1016/j.jncc.2025.02.007","DOIUrl":"10.1016/j.jncc.2025.02.007","url":null,"abstract":"<div><div>With the rapid progression of chemotherapies, the occurrence of chemoresistance is becoming a major obstacle in contemporary cancer treatment. As essential organelles, mitochondria perform diverse functions to provide ATP and various intermediates to modulate biosynthetic and bioenergetic processes, which are indispensable to cell survival. Recently, mitochondria have increasingly intrigued researchers for their unique influence on chemoresistance. This review explores the intricate relationship between mitochondria and chemoresistance. We delve into the complex roles that mitochondria play in chemoresistance, focusing on the aberrant alterations in mitochondrial behaviors and interactions with other organelles. We also review the subsequent impact of mitochondrial changes on cellular functions, such as metabolic reprogramming and the dysregulation of cell death. By presenting a retrospective analysis of previous research and elucidating the underlying mechanisms, we aim to reveal the potential of enhancing the efficacy of chemotherapies and overcoming cancer chemoresistance by targeting mitochondria. Hopefully, this review will provide directions for future research and the development of more viable drugs, ultimately improving the prognosis of cancer patients.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 453-473"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate cancer in China: epidemiological trends, genomic insights, and future directions for optimized management","authors":"Zhongyuan Wang ,&nbsp;Wenhao Xu ,&nbsp;Fangning Wan ,&nbsp;Xi Tian ,&nbsp;Aihetaimujiang Anwaier ,&nbsp;Shiqi Ye ,&nbsp;Siqi Zhou ,&nbsp;Hailiang Zhang ,&nbsp;Xiaojian Qin ,&nbsp;Dingwei Ye","doi":"10.1016/j.jncc.2025.05.002","DOIUrl":"10.1016/j.jncc.2025.05.002","url":null,"abstract":"<div><div>The incidence and mortality of prostate cancer (PCa) in China have risen sharply in recent years, posing an escalating public health concern. In contrast to Western populations, Chinese patients are more frequently diagnosed at advanced stages, often with metastatic disease and suboptimal survival outcomes. These disparities reflect intrinsic differences in epidemiological patterns, molecular landscapes, and healthcare delivery systems unique to the Chinese context. Nevertheless, prevailing PCa management paradigms, largely derived from Western-centric evidence, remain inadequately calibrated to the biological and clinical realities of Chinese patients. This review provides a comprehensive synthesis of the epidemiology, genomic alterations, clinical presentations, and treatment disparities of PCa in China, highlighting the urgent need for population-specific strategies. Priority areas include the development of ethnically optimized screening protocols, the integration of precision medicine approaches, and the implementation of regionally adapted prevention and early detection programs. Furthermore, expanding participation in clinical trials and accelerating translational research efforts, particularly in multi-omics and biomarker discovery, will be critical to bridging current gaps. By aligning emerging scientific innovations with localized healthcare needs, China holds the potential to reshape its prostate cancer care paradigm, improving outcomes, reducing disparities, and contributing to the global advancement of precision oncology.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 474-485"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term exposure to ozone and incidence of lung cancer in China: data based on a national population cohort (ChinaHEART)","authors":"Yi Wu ,&nbsp;Chunqi Wang ,&nbsp;Chunxiao Xu ,&nbsp;Siming Wang ,&nbsp;Rongshou Zheng ,&nbsp;Chunying Lin ,&nbsp;Xiaoyan Zhang ,&nbsp;Bowang Chen ,&nbsp;Yang Yang ,&nbsp;Wei Li ,&nbsp;Guangda He ,&nbsp;Jianlan Cui ,&nbsp;Wei Xu ,&nbsp;Lijuan Song ,&nbsp;Hao Yang ,&nbsp;Wenyan He ,&nbsp;Yan Zhang ,&nbsp;Jing Wei ,&nbsp;Tiantian Li ,&nbsp;Xi Li","doi":"10.1016/j.jncc.2025.06.005","DOIUrl":"10.1016/j.jncc.2025.06.005","url":null,"abstract":"<div><h3>Objective</h3><div>Ozone (O₃) is recognized as a predominant and increasingly prevalent gaseous pollutant contributing to the Global Burden of Disease. However, its effect on the development of lung cancer has not been adequately acknowledged.</div></div><div><h3>Methods</h3><div>Based on Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART), a nationwide, population-based cohort study, 2,006,878 participants living in 20,159 communities or villages were passively followed for the incidence of lung cancer through a linkage of data with the National Central Cancer Registry. The average O₃ levels over ten years from the year of enrolment in their respective localities were determined based on geographic coordinates. We conducted Cox proportional-hazards regression models to assess the independent hazard ratios (HRs) associated with O₃ exposure and the development of lung cancer.</div></div><div><h3>Results</h3><div>During the follow-up of 4.93 million person-years, 4555 new cases of lung cancer were identified. After adjusting for participant characteristics and other environmental factors, we observed a significant positive association between ambient O₃ exposure and lung cancer. Compared with participants in the quartile 1 of O₃, HRs and 95 % confidence intervals (CI) for the other three quartiles were 1.09 (95 % CI: 1.00–1.17), 1.17 (95 % CI: 1.06–1.29) and 1.42 (95 % CI: 1.26–1.59), respectively.</div></div><div><h3>Conclusions</h3><div>Long-term exposure to ambient O₃ is associated with a substantially higher risk of lung cancer. Further studies are needed to explore its pathogenic mechanisms, as well as to evaluate measures for exposure protection or harm mitigation at the individual or population level.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 486-492"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The multifaceted impact of circadian disruption on cancer risk: a systematic review of insights and economic implications","authors":"Vicente Javier Clemente-Suarez ,&nbsp;Eduardo Navarro-Jiménez ,&nbsp;Juan Camilo Benitez-Agudelo ,&nbsp;Ana Isabel Beltrán-Velasco ,&nbsp;Pedro Belinchón-deMiguel ,&nbsp;Domingo Jesús Ramos-Campo ,&nbsp;Carlota Valeria Villanueva-Tobaldo ,&nbsp;Alexandra Martín-Rodríguez ,&nbsp;Jose Francisco Tornero-Aguilera","doi":"10.1016/j.jncc.2025.04.005","DOIUrl":"10.1016/j.jncc.2025.04.005","url":null,"abstract":"<div><h3>Background</h3><div>Circadian disruption has emerged as a significant risk factor for cancer, driven by mechanisms such as hormonal imbalances, impaired DNA repair, immune suppression, and metabolic dysregulation. Modern societal patterns—shift work, artificial light at night, and irregular sleep schedules—have exacerbated these risks.</div></div><div><h3>Methods</h3><div>We conducted a systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, screening over 500 studies published between 2003 and 2023 from PubMed, Scopus, Embase, ScienceDirect, and Web of Science. Inclusion criteria focused on peer-reviewed epidemiological and mechanistic studies linking circadian disruption with cancer risk. The Newcastle-Ottawa Scale was used for methodological quality assessment.</div></div><div><h3>Results</h3><div>A total of 75 high-quality studies were included. Strong evidence supports associations between circadian disruption and breast, prostate, and colorectal cancers, with limited but emerging evidence for melanoma and bladder cancer. Mechanistic pathways involve melatonin suppression, dysregulation of CLOCK and BMAL1 genes, reduced natural killer cell activity, and chronic inflammation due to metabolic imbalance. Light-at-night (LAN) exposure and prolonged night shift work were consistently identified as major risk factors. Furthermore, economic analyses reveal a substantial burden due to increased healthcare costs and productivity losses, particularly in shift work-dominated sectors.</div></div><div><h3>Conclusions</h3><div>Circadian misalignment is a critical, yet often overlooked, contributor to cancer incidence and associated economic burdens. Public health strategies—such as regulating shift schedules, reducing LAN exposure, and promoting chronotherapy—are essential to mitigate these risks. Further research should address sex-based differences, improve exposure measurement, and extend investigations to low- and middle-income countries.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 524-536"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromuscular complications associated with cancer immunotherapy","authors":"Ge Xiong ,&nbsp;Catherine Lomen-Herth ,&nbsp;David Richman ,&nbsp;Tianhong Li","doi":"10.1016/j.jncc.2025.05.004","DOIUrl":"10.1016/j.jncc.2025.05.004","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) and cellular immunotherapy have revolutionized cancer treatment. Although these therapies have significantly improved cancer patients’ survival, they are associated with a range of immune-related adverse events (irAEs) that can affect patients' quality of life. Neuromuscular complications related to cancer immunotherapy are rare (&lt;5 % with monotherapy and up to 14 % with combination therapy), but they can be fatal if not addressed promptly. Early diagnosis and intervention are crucial to improving the quality of life and survival of cancer patients affected by neuromuscular complications associated with immunotherapy. However, symptoms can be diverse and nonspecific, including weakness, numbness, imbalance, dysarthria, dysphagia, and even difficulty in breathing, which presents significant challenges for diagnosis and management. This review summarizes the current understanding of the mechanisms, clinical features, diagnostic challenges, and management strategies for neuromuscular complications related to cancer immunotherapy. Understanding the complex interplay between T cells, B cells, and cytokines in the pathogenesis of neuromuscular irAEs is essential for guiding their management. It is important for healthcare providers, including oncologists, neurologists, primary care physicians, and other practitioners, to be familiar with the multidisciplinary clinical management of neuromuscular irAEs. This knowledge will help reduce the mortality and morbidity associated with these complications.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 441-452"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Score-based prediction model for female hepatocellular carcinoma surveillance in asymptotic HBsAg carriers: a multicenter cohort study in China","authors":"Mengdi Cao ,&nbsp;Maomao Cao ,&nbsp;Changfa Xia ,&nbsp;Fan Yang ,&nbsp;Xinxin Yan ,&nbsp;Siyi He ,&nbsp;Shaoli Zhang ,&nbsp;Yi Teng ,&nbsp;Qianru Li ,&nbsp;Nuopei Tan ,&nbsp;Jiachen Wang ,&nbsp;Chunfeng Qu ,&nbsp;Wanqing Chen","doi":"10.1016/j.jncc.2025.05.005","DOIUrl":"10.1016/j.jncc.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Existing hepatocellular carcinoma (HCC) prediction models lack transferability and generalizability when applied to female populations, resulting in diminished performance and inadequate tools for accurate HCC risk stratification among females. This study aims to develop and validate a score-based prediction model for early detection of HCC in female hepatitis B surface antigen (HBsAg) carriers.</div></div><div><h3>Methods</h3><div>Participants were recruited from a multicenter prospective cohort engaged in liver cancer screening across China including seven high-risk rural areas and one additional high-risk rural area. The study involved 7080 females as the derivation cohort and 2069 as the validation cohort, with all participants aged 35–70 years and HBsAg positive. Laboratory tests and epidemiological surveys were conducted. Key predictor variables were identified through LASSO regression analysis, and score-based prediction models were developed based on Cox proportional hazards model. Model performance including discrimination and calibration was evaluated, and compared to existing prediction models and screening strategies.</div></div><div><h3>Results</h3><div>After a median follow-up of 3.69 and 5.42 years, 147 and 45 HCC cases were identified in the derivation and validation cohorts, respectively. The female HCC (HCCF) model incorporating five independent variables: age, α-fetoprotein (AFP), albumin, alanine aminotransferase, and platelet, showed excellent performance with an area under the receiver operating characteristic curve (AUC) of 0.82 (95 % CI: 0.78–0.86). The HCCF-Enhanced model which included cirrhosis, achieved an AUC of 0.85 (95 % CI: 0.81–0.89). Both models demonstrated superior predictive performance than existing models, with strong predictive accuracy in the validation cohort: AUCs of 0.83 (95 % CI: 0.77–0.89) and 0.88 (95 % CI: 0.83–0.92), respectively. The HCCF model, at a score threshold of 7, achieved the largest Youden’s index and identified 32.80 % of high-risk individuals. When combined with ultrasonography (US), the model detected 37 additional cases, significantly improved screening sensitivity and accuracy compared to the traditional AFP plus US strategy.</div></div><div><h3>Conclusions</h3><div>The developed HCCF models with good performance for HCC prediction in HBsAg-positive females significantly improve screening efficiency and provide an effective tool for surveillance, ultimately helping to optimize prevention and management strategies for HCC.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 493-500"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial and maturity heterogeneity of tertiary lymphoid structures shapes immune microenvironment and progression in prostate cancer","authors":"Zhongyuan Wang ,&nbsp;Qintao Ge ,&nbsp;Ren Mo ,&nbsp;Jiahe Lu ,&nbsp;Xi Tian ,&nbsp;Aihetaimujiang Anwaier ,&nbsp;Shiqi Ye ,&nbsp;Siqi Zhou ,&nbsp;Weihang Guo ,&nbsp;Chuanhai Cai ,&nbsp;Jianfeng Yang ,&nbsp;Hailiang Zhang ,&nbsp;Xiaojian Qin ,&nbsp;Dingwei Ye ,&nbsp;Wenhao Xu","doi":"10.1016/j.jncc.2025.06.003","DOIUrl":"10.1016/j.jncc.2025.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Tertiary lymphoid structure (TLS), ectopic lymphoid aggregates formed in response to chronic inflammation, have emerged as potential prognostic biomarkers and mediators of anti-tumor immunity in various cancers. However, the heterogeneity of TLS spatial distribution, maturity, and their prognostic and immunological significance in prostate cancer (PCa) remain poorly characterized.</div></div><div><h3>Methods</h3><div>We utilized immunohistochemistry, multispectral fluorescence immunohistochemistry (mIHC) and spatial multi-omics analyses to evaluate the heterogeneity of TLS and its relationship with immune components in the tumor microenvironment (TME). Prognostic implications were assessed in 701 PCa patients from the TCGA and Fudan University Shanghai Cancer Center cohorts. The association between TLS heterogeneity and immunoreactivity was assessed through the quantification of immune cell infiltration. CellTreck and robust cell type decomposition deconvolution algorithms were used to decipher the colocalization features of each cell, cell-cell communication and ligand-receptor features within TLS regions.</div></div><div><h3>Results</h3><div>In PCa, TLSs were detected in approximately 20 % of patients across both cohorts, with intratumoral TLS (intra-TLS) being twice as prevalent as peritumoral TLS (peri‑TLS). Patients harboring intra-TLS exhibited significantly longer disease-free and progression-free survival. Compared to peri‑TLS, intra-TLS were more mature, characterized by increased T-effector cell infiltration, activation of interferon pathways, and the presence of follicular dendritic cell centers and B cell aggregates. Notably, compared with immature TLS, mature TLS were markedly associated with reduced PD-L1 expression, lower regulatory T cells (Tregs) infiltration, and increased high endothelial venules (HEVs) density, indicative of an immunologically active microenvironment. Spatial multi-omics analysis revealed that mature TLS exhibited enriched immune cell diversity and HEVs density, suggesting enhanced anti-tumor immunity. Furthermore, cell-cell communication analysis identified significant interactions between CCL5⁺ dendritic cells and ACKR1⁺ activated B cells within mature TLS, reflecting the enhanced capacity of mature TLS to orchestrate robust antigen presentation and B-cell-driven immune responses.</div></div><div><h3>Conclusions</h3><div>In conclusion, this study highlights the prognostic and immunological implications of TLS heterogeneity in PCa, demonstrating that the spatial distribution and maturity of TLSs are closely linked to TME activation and improved clinical outcomes. These findings provide novel insights into the immune landscape of PCa and establish a foundation for immune-based precision stratification and therapeutic development.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 501-514"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic predictors of prostate cancer recurrence following focal cryotherapy: a pooled analysis of phase II trial and prospective cohort data","authors":"Kae Jack Tay ,&nbsp;Boon Hao Hong ,&nbsp;Enya Hui Wen Ong ,&nbsp;Kah Min Tan ,&nbsp;Gianella Cabuhat Pacho ,&nbsp;Samantha Jingxuan Wong ,&nbsp;Yu Guang Tan ,&nbsp;Yan Mee Law ,&nbsp;Nye Thane Ngo ,&nbsp;Puay Hoon Tan ,&nbsp;John S.P. Yuen ,&nbsp;Henry S.S. Ho ,&nbsp;Kenneth Chen ,&nbsp;Jiping Peng ,&nbsp;Clare Wei Tian Foo ,&nbsp;Xin Xiu Sam ,&nbsp;Jeffrey K.L. Tuan ,&nbsp;Ravindran Kanesvaran ,&nbsp;Rajan T. Gupta ,&nbsp;Steven Rozen ,&nbsp;Melvin Lee Kiang Chua","doi":"10.1016/j.jncc.2025.04.002","DOIUrl":"10.1016/j.jncc.2025.04.002","url":null,"abstract":"<div><h3>Objective</h3><div>Focal therapy (FT) is a potential treatment option for limited-volume clinically-significant prostate cancer (csPCa). However, despite rigorous selection, approximately 20% of patients experience early failure. We investigated the association of transcriptomic profiles and csPCa recurrence post-FT.</div></div><div><h3>Methods</h3><div>52 men from a phase II trial (NCT04138914) and a prospective observational cohort underwent focal cryotherapy for csPCa. Patients underwent multiparametric magnetic resonance imaging, and targeted and systematic-saturation biopsy before- and 1-year post-FT. Recurrence was defined as grade-group (GG) ≥2 cancer in the 1-year post-FT biopsy. Pre-treatment lesions were profiled using the Decipher genomic classifier (GC). GC scores, luminal-basal status, tumor microenvironment and cancer hallmark pathways were correlated with csPCa recurrence.</div></div><div><h3>Results</h3><div>Median PSA was 7.0 ng/dl; 37/52 (71.1%) men had GG2, 12/52 (23.1%) GG3, and 3/52 (5.8%) GG4 cancer. Recurrence was observed in 9/52 (17.3%) men. Median GC score was higher in patients with recurrence (0.60 <em>vs</em> 0.38, <em>P</em> = 0.014) and remained significantly associated with recurrence after adjustment for GG (adjusted <em>OR</em>: 1.37 [95% CI: 1.01–1.93], <em>P</em> = 0.04). Luminal-proliferative tumors based on the prostate cancer-specific subtyping classifier (PSC) had more csPCa recurrence compared with luminal-differentiated (LD) and basal subtypes (30.4% <em>vs</em> 0% [LD] <em>vs</em> 15.4% [basal-neuroendocrine] and 14.3% [basal-immune], <em>P</em> = 0.027). Higher expression of DNA repair pathway was also associated with recurrence (<em>OR</em>: 2.12 [95% CI: 1.09–4.57], <em>P</em> = 0.025).</div></div><div><h3>Conclusions</h3><div>Higher GC score is associated with risk of csPCa recurrence post-FT. Patients with GC low-risk and PSC-LD csPCa may represent the ideal subgroup for FT. Prospective validation in a large cohort is warranted.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 515-523"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}