{"title":"The global progress and quality assessment of research on the association between circulating tumor DNA and clinical prognosis: a systematic review","authors":"Meng Zhang , Xiaowei Chen , Qingxin Zhou , Nana Guo , Baoshan Cao , Hongmei Zeng , Wanqing Chen , Feng Sun","doi":"10.1016/j.jncc.2024.10.002","DOIUrl":"10.1016/j.jncc.2024.10.002","url":null,"abstract":"<div><h3>Objective</h3><div>Circulating tumor DNA (ctDNA) has shown potential as a prognostic biomarker in patients with solid tumors. This study aimed to systematically summarize the global application of ctDNA in the prognostic management of solid tumor patients and to evaluate the quality of the current studies.</div></div><div><h3>Methods</h3><div>PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched to collect cohort studies on ctDNA in the prognosis of solid tumor patients from January 2016 to May 2022. The language was limited to English. Information including general information, participants and cancer characteristics, ctDNA and outcome information were extracted. The quality of the studies was assessed using the Newcastle–Ottawa Scale checklist.</div></div><div><h3>Results</h3><div>A total of 214 studies were included in the final analysis, encompassing 21,076 patients. The number of studies has increased annually from 2016 to 2022. The most common types of solid tumors studied were colorectal cancer (27.10 %), lung cancer (20.09 %), pancreatic cancer (16.82 %), and breast cancer (14.02 %). The top three journals by number of publications had an impact factor in 2023 greater than 10. Of the studies, the median sample size was 69 (interquartile range: 41–111), 69.81 % had a sample size <100, 68.92 % had a median/mean age ≥60 years, and 74.05 % were from developed countries. Multi-center studies accounted for 40.36 %. Additionally, 29.82 % of the studies had a bias risk score ≤6. Only 16.67 % of studies on liver cancer had a bias risk score >6. The primary criteria not met by the studies included “Adequacy of follow-up of cohorts” (33.33 %), “Assessment of outcome” (32.16 %) and “Representativeness of the exposed cohort” (27.49 %).</div></div><div><h3>Conclusions</h3><div>The prognostic value of ctDNA in patients with solid tumors is gaining increasing attention, leading to a steady rise in the number of studies. However, many studies still suffer from small sample sizes and a lack of representativeness. Furthermore, details regarding ctDNA detection methods and results reporting are often insufficiently described. There is an urgent need to improve the quality of such research.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 156-166"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816234","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}
Weiwei Chen , Li Yang , Victor Ho-fun Lee , Liangliang Xu , Lingyu Ma , Zhenghao Ye , Wanli Xu , Caining Zhao , Danyang Zheng , Karrie Mei-Yee Kiang , Stella Sun , Yuan Qu , Jiandong Zha , Dazhi Pang , Yan Zhang , Zhibing Liang , Wenchu Lin , Jinliang Zhang , Jitian Zhang , Min Luo , Feng-Ming (Spring) Kong
{"title":"Indoleamine 2,3-dioxygenase 1-mediated immune suppressive status is positively associated with brain metastasis in patients with non-small cell lung cancer","authors":"Weiwei Chen , Li Yang , Victor Ho-fun Lee , Liangliang Xu , Lingyu Ma , Zhenghao Ye , Wanli Xu , Caining Zhao , Danyang Zheng , Karrie Mei-Yee Kiang , Stella Sun , Yuan Qu , Jiandong Zha , Dazhi Pang , Yan Zhang , Zhibing Liang , Wenchu Lin , Jinliang Zhang , Jitian Zhang , Min Luo , Feng-Ming (Spring) Kong","doi":"10.1016/j.jncc.2024.12.004","DOIUrl":"10.1016/j.jncc.2024.12.004","url":null,"abstract":"<div><h3>Background</h3><div>Indoleamine 2,3-dioxygenase (IDO1) activity, measured by kynurenine/tryptophan (K:T) ratio, is known for its association with distant metastasis and overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Here, we aimed to examine whether IDO1 activity is correlated with OS in NSCLC patients with brain metastasis (Bramet) and has negative effect on modulating the anti-tumor functions of immune cells.</div></div><div><h3>Methods</h3><div>This study was a part of a prospective clinical trial in circulating biomarkers. Blood or tissues from eligible participants were collected for measurement of kynurenine, tryptophan, immune cell subtype, scRNA-seq analysis, and untargeted metabolomics analysis.</div></div><div><h3>Results</h3><div>A total of 195 patients were enrolled. The median kynurenine to tryptophan (K:T) ratio was 0.18, with consistent values observed among patients with NSCLC Bramet and those without (0.18 and 0.11, respectively). Notably, student's t-test analysis revealed significantly higher kynurenine concentrations in stage IV patients compared to those in stage I (2.3 vs 1.7 µM, <em>P</em> < 0.001). In patients with Bramet, both kynurenine concentrations and K:T ratios were significantly elevated in comparison with those of extra-cerebral metastasis (2.7 vs 1.9 µM, <em>P</em> < 0.001; 0.12 vs 0.095, <em>P</em> = 0.028; respectively). Single-cell analysis further validated a high level of IDO1 expression in stage IV tumors or Bramet lesions, particularly in macrophages, regulated by chemokines such as CXCL11. Additionally, K:T ratios exhibited significant associations with Treg cell percentages and OS in patients with Bramet (<em>P</em> = 0.039). Treatment with kynurenine led to the upregulation of immune-suppressive molecules, including PD-1, in T cells. Finally, untargeted metabolomics analysis further identified that, apart from the IDO1 metabolic pathway, other metabolites, such as those involved in phospholipid pathways, were also implicated in Bramet.</div></div><div><h3>Conclusion</h3><div>IDO1 metabolites may play immune-suppressive roles in NSCLC patients with Bramet.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 179-192"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816299","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":"Ammonia-induced lysosomal and mitochondrial damage: a novel perspective on T cell-based cancer immunotherapy","authors":"Jianqiao Shentu , Hening Xu , Feng Zhu","doi":"10.1016/j.jncc.2025.01.004","DOIUrl":"10.1016/j.jncc.2025.01.004","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 105-107"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816369","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":"Lifetime risk of developing and dying from cancer in Henan Province, China: current status, temporal trends, and disparities","authors":"Qiong Chen, Shuzheng Liu, Yin Liu, Hongwei Liu, Hong Wang, Lanwei Guo, Huifang Xu, Xiaoli Guo, Xiaoyang Wang, Ruihua Kang, Liyang Zheng, Shaokai Zhang","doi":"10.1016/j.jncc.2024.11.005","DOIUrl":"10.1016/j.jncc.2024.11.005","url":null,"abstract":"<div><h3>Objective</h3><div>To understand the current status and changing trends in the lifetime risk of residents in Henan Province, China to develop and die from cancer.</div></div><div><h3>Methods</h3><div>Lifetime risk was estimated using the Adjusted for Multiple Primaries (AMP) method, incorporating cancer incidence, mortality, and all-cause mortality data from 55 cancer registries in Henan Province, China. Estimates were calculated overall and stratified by gender and area. The annual percent change (APC) in lifetime risk from 2010 to 2020, stratified by gender and cancer site, was estimated using a log-linear model.</div></div><div><h3>Results</h3><div>In 2020, the lifetime risk of developing and dying from cancer was 30.19 % (95 % CI: 29.63 %–30.76 %) and 23.62 % (95 % CI: 23.28 %–23.95 %), respectively. These estimates were higher in men, with values of 31.22 % (95 % CI: 30.59 %–31.85 %) for developing cancer and 26.73 % (95 % CI: 26.29 %–27.16 %) for dying from cancer, compared with women, who had values of 29.02 % (95 % CI: 28.12 %–29.91 %) and 20.08 % (95 % CI: 19.51 %–20.64 %), respectively. There were also geographical differences, with higher estimates in urban areas compared with rural areas. Residents had the highest lifetime risk of developing lung cancer, with a rate of 6.94 %, followed by breast cancer (4.14 %), stomach cancer (3.95 %), esophageal cancer (3.75 %), and liver cancer (2.86 %). Similarly, the highest lifetime risk of dying from cancer was observed for the following sites: lung (5.99 %), stomach (3.60 %), esophagus (3.39 %), liver (2.78 %), and colorectum (1.55 %). Overall, the lifetime risk of developing cancer increased, with an APC of 0.75 % (<em>P</em> < 0.05). Varying trends were observed across different cancer sites. There were gradual decreases in nasopharynx, esophagus, stomach, and liver cancers. Conversely, increasing trends were noted for most other sites, with the highest APCs observed in thyroid, prostate, lymphoma, kidney, and gallbladder cancers.</div></div><div><h3>Conclusion</h3><div>The lifetime risks of developing and dying from cancer were 30.19 % and 23.62 %, respectively. Variations in cancer risk across different regions, genders, specific cancer sites, and over calendar years provide important information for cancer prevention and policy making in the population.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 140-148"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816220","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}
Xiaoying Huang , Minghao Qin , Mengjie Fang , Zipei Wang , Chaoen Hu , Tongyu Zhao , Zhuyuan Qin , Haishan Zhu , Ling Wu , Guowei Yu , Francesco De Cobelli , Xuebin Xie , Diego Palumbo , Jie Tian , Di Dong
{"title":"The application of artificial intelligence in upper gastrointestinal cancers","authors":"Xiaoying Huang , Minghao Qin , Mengjie Fang , Zipei Wang , Chaoen Hu , Tongyu Zhao , Zhuyuan Qin , Haishan Zhu , Ling Wu , Guowei Yu , Francesco De Cobelli , Xuebin Xie , Diego Palumbo , Jie Tian , Di Dong","doi":"10.1016/j.jncc.2024.12.006","DOIUrl":"10.1016/j.jncc.2024.12.006","url":null,"abstract":"<div><div>Upper gastrointestinal cancers, mainly comprising esophageal and gastric cancers, are among the most prevalent cancers worldwide. There are many new cases of upper gastrointestinal cancers annually, and the survival rate tends to be low. Therefore, timely screening, precise diagnosis, appropriate treatment strategies, and effective prognosis are crucial for patients with upper gastrointestinal cancers. In recent years, an increasing number of studies suggest that artificial intelligence (AI) technology can effectively address clinical tasks related to upper gastrointestinal cancers. These studies mainly focus on four aspects: screening, diagnosis, treatment, and prognosis. In this review, we focus on the application of AI technology in clinical tasks related to upper gastrointestinal cancers. Firstly, the basic application pipelines of radiomics and deep learning in medical image analysis were introduced. Furthermore, we separately reviewed the application of AI technology in the aforementioned aspects for both esophageal and gastric cancers. Finally, the current limitations and challenges faced in the field of upper gastrointestinal cancers were summarized, and explorations were conducted on the selection of AI algorithms in various scenarios, the popularization of early screening, the clinical applications of AI, and large multimodal models.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 113-131"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816323","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":"Advance and challenge of DNA methylation as cancer biomarkers for risk stratification, screening and early detection","authors":"Na Li , Kai Song , Hongda Chen , Min Dai","doi":"10.1016/j.jncc.2024.12.007","DOIUrl":"10.1016/j.jncc.2024.12.007","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 108-112"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816370","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":"Projections of esophageal cancer incidence trend in Jiangsu Province, China: a Bayesian modeling study","authors":"Weigang Miao, Yuanyuan Feng, Bijia Jiang, Yanan Wan, Xikang Fan, Renqiang Han, Jinyi Zhou","doi":"10.1016/j.jncc.2024.11.004","DOIUrl":"10.1016/j.jncc.2024.11.004","url":null,"abstract":"<div><h3>Objective</h3><div>Esophageal cancer has made a great contribution to the cancer burden in Jiangsu Province, East China. This study was aimed at reporting esophageal cancer incidence trend in 2009–2019 and its prediction to 2030.</div></div><div><h3>Methods</h3><div>The burden of esophageal cancer in Jiangsu in 2019 was estimated using 54 cancer registries’ data selected from Jiangsu Cancer Registry. Incident cases of 16 cancer registries were applied for the temporal trend from 2009 to 2019. The burden of esophageal cancer by 2030 was projected using the Bayesian age-period-cohort (BAPC) model.</div></div><div><h3>Results</h3><div>About 24,886 new cases of esophageal cancer (17,233 males and 7,653 females) occurred in Jiangsu in 2019. Rural regions of Jiangsu had the highest incidence rate. The age-standardized incidence rate (ASIR, per 100,000 population) of esophageal cancer in Jiangsu decreased from 27.72 per 100,000 in 2009 to 14.18 per 100,000 in 2019. The BAPC model showed that the ASIR would decline from 13.01 per 100,000 in 2020 to 4.88 per 100,000 in 2030.</div></div><div><h3>Conclusions</h3><div>According to the data, esophageal cancer incidence rates were predicted to decline until 2030, yet the disease burden is still significant in Jiangsu. The existing approaches to prevention and control are effective and need to be maintained.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 149-155"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816221","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}
Zhentao Fu , Fan Jiang , Zilong Lu , Jie Chu , Xiaohui Xu , Bingying Zhang , Xiaolei Guo , Aiqiang Xu , Jixiang Ma
{"title":"Changes in cancer mortality in Shandong Province, China: a large population based study","authors":"Zhentao Fu , Fan Jiang , Zilong Lu , Jie Chu , Xiaohui Xu , Bingying Zhang , Xiaolei Guo , Aiqiang Xu , Jixiang Ma","doi":"10.1016/j.jncc.2024.08.002","DOIUrl":"10.1016/j.jncc.2024.08.002","url":null,"abstract":"<div><h3>Objective</h3><div>To analyze the trend of major malignant tumor mortality in Shandong Province, eastern China from 1970 to 2021, and to provide the scientific basis for malignant tumor prevention and control.</div></div><div><h3>Methods</h3><div>Cancer mortality data were sourced from three nationwide cause-of-death surveys and the Shandong Death Registration System. Trends in overall mortality and major causes of death were elucidated through indicators such as mortality rates and age-adjusted death rates, by comparing findings from the three comprehensive mortality surveys and the Shandong Death Registration System. The difference decomposing method was employed to estimate the contributions of non-demographic and demographic factors to the observed changes in cancer mortality.</div></div><div><h3>Results</h3><div>From 1970 to 2021, the crude mortality rate of malignant tumors witnessed an overall increase in Shandong Province. The age-standardized mortality rate initially rose before subsequently declining. The proportion of cancer deaths among all causes of death increased initially and then stabilized at a high level of approximately 25 %. Both non-demographic and demographic factors played a role in the rise of the crude cancer mortality rate, with the proportion attributed to demographic factors gradually surpassing that of non-demographic factors. Despite the continuous increase in the crude mortality rate, the adjusted mortality rate exhibited a downward trend since 1990. Significant changes were observed in the ranking of the mortality rates of major cancers. For example, the mortality rate of lung cancer exhibited a continuous upward trajectory, ascending from the fifth to the first place and marking a 7.69-fold increase from 1970 to 2021. Conversely, digestive system tumors, including gastric cancer, esophageal cancer, and liver cancer, displayed varying degrees of decline, particularly in the standardized rates, which demonstrated a notable downward trend since 1990. The crude mortality rate of colorectal cancer and breast cancer showed an obvious upward trend, but the standardized rate did not rise significantly. For cervical cancer, both the crude and adjusted mortality rates displayed a pattern of initially decreasing and then increasing.</div></div><div><h3>Conclusions</h3><div>Malignant tumors remain a significant threat to the residents of Shandong Province. The changing trends in various malignant tumors are inconsistent, underscoring the need for tailored intervention strategies to effectively control different types of malignant tumors.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 132-139"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816219","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}
Xi Yang , Yuanyuan Zhang , Shuangzheng Jia , Yong Yang , Jie Zhu , Wei Li , Lingying Wu , Jusheng An , Manni Huang
{"title":"The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTs","authors":"Xi Yang , Yuanyuan Zhang , Shuangzheng Jia , Yong Yang , Jie Zhu , Wei Li , Lingying Wu , Jusheng An , Manni Huang","doi":"10.1016/j.jncc.2024.08.003","DOIUrl":"10.1016/j.jncc.2024.08.003","url":null,"abstract":"<div><h3>Objective</h3><div>A conventional endpoint for locally advanced cervical cancer (LACC) clinical trials is overall survival (OS) with five years of follow-up. The primary hypothesis was that progression-free survival (PFS) with three years of follow-up (PFS36) would be an appropriate primary surrogate endpoint.</div></div><div><h3>Materials and methods</h3><div>The primary hypothesis, which was developed from our data, was further investigated using phase III randomized controlled trials and then externally validated using retrospective studies up to 2023. Correlation analysis at the treatment-arm level was performed between 2-, 3-, 4-, and 5-year PFS rates and 5-year OS.</div></div><div><h3>Results</h3><div>A total of 613 patients with histologically confirmed cervical cancer who underwent radiotherapy or chemoradiation at our institute between January 2010 and December 2013 were eligible. The recurrence rates for years 1 through 5 were 12.9%, 7.3%, 3%, 2.3%, and 1.8%, respectively. Patients who did not achieve PFS36 had a 5-year OS rate of 30.3%. However, patients who achieved PFS36 had a 5-year OS rate of 98.2%. Further data were extracted from 26 randomized phase III trials on LACC. The trials included 55 arms, with a pooled sample size of 7,281 patients. Trial-level surrogacy results revealed that PFS36 (r<sup>2</sup>, 0.732) was associated with 5-year OS. The correlation between PFS36 and OS was externally validated using independent retrospective data.</div></div><div><h3>Conclusion</h3><div>A significant positive correlation was found between PFS36 and OS at 5 years of follow-up both within patients and across trials. These results suggest that PFS36 is an appropriate endpoint for LACC clinical trials of radiotherapy-based regimens.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 193-202"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816300","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}
Xiaomei Zhang , Zailin Yang , Xiaoqing Xie , Jun Li , Qing Xiao , Guofa Xu , Ben Ma , Xudong Xie , Yi Liu , Liuyue Zhai , Yifeng Tang , Huihui Fu , Sanxiu He , Tingting Liu , Dehong Huang , Censi Zeng , Yixing Zhou , Renzhi Hu , Binling Guo , Chaoyu Wang , Yao Liu
{"title":"The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma","authors":"Xiaomei Zhang , Zailin Yang , Xiaoqing Xie , Jun Li , Qing Xiao , Guofa Xu , Ben Ma , Xudong Xie , Yi Liu , Liuyue Zhai , Yifeng Tang , Huihui Fu , Sanxiu He , Tingting Liu , Dehong Huang , Censi Zeng , Yixing Zhou , Renzhi Hu , Binling Guo , Chaoyu Wang , Yao Liu","doi":"10.1016/j.jncc.2025.02.001","DOIUrl":"10.1016/j.jncc.2025.02.001","url":null,"abstract":"<div><h3>Background</h3><div>Human immunodeficiency virus (HIV)-associated lymphomas (HAL), mainly aggressive B-cell lymphomas, pose a significant challenge in cancer research due to their multifaceted pathogenesis and aggressive clinical course. Despite the clinical importance, the genomic and immune characteristics of these lymphomas remain poorly elucidated.</div></div><div><h3>Methods</h3><div>We employed single-cell RNA sequencing (scRNA-seq) on lymph node samples from aggressive B-cell lymphomas, mainly including 6 cases of diffuse large B-cell lymphoma (DLBCL) and 5 cases of Burkitt lymphoma (BL) from people living with HIV (PLWH), along with 3 DLBCL cases from individuals without HIV for comparison.</div></div><div><h3>Results</h3><div>Malignant B cells in HAL consistently exhibited high proliferative and oxidative phosphorylation (OXPHOS)-type metabolic signatures. Moreover, these cells demonstrated loss expression of major histocompatibility complex class I (MHC-I), strategically reducing tumor immunogenicity. HAL harbors special populations of naive and atypical memory B cells that exhibited high metabolic and immune-activated transcriptional profiles. Additionally, HAL exhibited senescence-like dysfunction in T cells, characterized by the reductions in regulatory activity of Treg and cytotoxic activity of CD8<sup>+</sup> T cells, as well as decreases expression of <em>IL7R</em> genes and increases expression of <em>FOS</em> and <em>FOSB</em> genes. Our immunofluorescence results showed that the cytotoxic CD8<sup>+</sup> T cells in HAL may have a dysfunction of lytic granule polarization. Furthermore, macrophages from HAL exhibited stronger immunosuppressive transcriptional characteristics, and a robust immunosuppressive SPP1-CD44 interaction was predicted between C1QA<sup>+</sup> macrophages and T cells.</div></div><div><h3>Conclusions</h3><div>Our findings clearly indicate that HAL differs significantly from non-HAL, ranging from malignant B cells to the immune microenvironment. This study provides a comprehensive single-cell atlas of HIV-associated aggressive B-cell lymphomas, offering new insights into aggressiveness and immune evasion observed in HAL.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 221-235"},"PeriodicalIF":7.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816810","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}