Journal of the National Cancer Center最新文献

{"title":"Changes in cancer mortality in Shandong Province, China: a large population based study","authors":"Zhentao Fu ,&nbsp;Fan Jiang ,&nbsp;Zilong Lu ,&nbsp;Jie Chu ,&nbsp;Xiaohui Xu ,&nbsp;Bingying Zhang ,&nbsp;Xiaolei Guo ,&nbsp;Aiqiang Xu ,&nbsp;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}

{"title":"Projections of esophageal cancer incidence trend in Jiangsu Province, China: a Bayesian modeling study","authors":"Weigang Miao,&nbsp;Yuanyuan Feng,&nbsp;Bijia Jiang,&nbsp;Yanan Wan,&nbsp;Xikang Fan,&nbsp;Renqiang Han,&nbsp;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}

{"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 ,&nbsp;Yuanyuan Zhang ,&nbsp;Shuangzheng Jia ,&nbsp;Yong Yang ,&nbsp;Jie Zhu ,&nbsp;Wei Li ,&nbsp;Lingying Wu ,&nbsp;Jusheng An ,&nbsp;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 (r², 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}

{"title":"The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma","authors":"Xiaomei Zhang ,&nbsp;Zailin Yang ,&nbsp;Xiaoqing Xie ,&nbsp;Jun Li ,&nbsp;Qing Xiao ,&nbsp;Guofa Xu ,&nbsp;Ben Ma ,&nbsp;Xudong Xie ,&nbsp;Yi Liu ,&nbsp;Liuyue Zhai ,&nbsp;Yifeng Tang ,&nbsp;Huihui Fu ,&nbsp;Sanxiu He ,&nbsp;Tingting Liu ,&nbsp;Dehong Huang ,&nbsp;Censi Zeng ,&nbsp;Yixing Zhou ,&nbsp;Renzhi Hu ,&nbsp;Binling Guo ,&nbsp;Chaoyu Wang ,&nbsp;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⁺ 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⁺ 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⁺ 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}

{"title":"Night shift work and breast cancer risk – 2023 update of epidemiologic evidence","authors":"Johnni Hansen,&nbsp;Julie Elbæk Pedersen","doi":"10.1016/j.jncc.2024.07.004","DOIUrl":"10.1016/j.jncc.2024.07.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Night shift work is a complex and frequent occupational exposure, and breast cancer stands as the most prevalent cancer in women. The International Agency for Research on Cancer (IARC) has twice classified night shift work as a probable breast carcinogen, with the latest classification in June 2019. Since that time, new epidemiologic data has emerged.</div></div><div><h3>Methods</h3><div>We searched PubMed for original articles based on cohort and case-control studies of “breast cancer and night shift work” published after the IARC evaluation in June 2019.</div></div><div><h3>Results</h3><div>In total six cohorts and four case-control studies were included in our review. Overall, we observed some support for associations between persistent (long duration or high frequency) night shift work and an increase in breast cancer risk, though most studies were relatively small and statistically under-powered. Moreover, the recent studies do not contribute further evidence regarding the interaction with menopausal status, diurnal preference, hormonal subtypes of breast cancer or gene-environment aspects, which were issues that were left from the IARC evaluation.</div></div><div><h3>Conclusions</h3><div>The available new results somewhat consolidate the epidemiological evidence from IARC's 2019 evaluation, and do not provide further evidence regarding interaction of interest, e.g. menopausal status, etc. Therefore, long term follow-up of prospective cohorts or nested case-control studies, including precise exposure assessment and examinations of relevant interactions such as menopausal status, diurnal preference, hormonal subtypes of breast cancer and gene-environment aspects, are warranted. Meanwhile, protective measures for the night workers should be considered.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 94-103"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer: a multicenter, open-label, non-inferiority, randomized controlled trial’ [Journal of the National Cancer Center 4 (2024) 135–141]","authors":"Rong Li ,&nbsp;Hongping Zhang ,&nbsp;Qingshui Li ,&nbsp;Guangwen Yuan ,&nbsp;Yanjie Zhou ,&nbsp;Rutie Yin ,&nbsp;He Wang ,&nbsp;Chunyan Wang ,&nbsp;Yi Huang ,&nbsp;Wei Wang ,&nbsp;Xiaojian Yan ,&nbsp;Lingying Wu ,&nbsp;Qi Zhou","doi":"10.1016/j.jncc.2024.11.002","DOIUrl":"10.1016/j.jncc.2024.11.002","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Page 93"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell spatial immune profiling for precision immunotherapy in Lynch syndrome","authors":"Ramadhani Chambuso ,&nbsp;Stephene S Meena","doi":"10.1016/j.jncc.2024.12.002","DOIUrl":"10.1016/j.jncc.2024.12.002","url":null,"abstract":"<div><div>Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) predisposition syndrome, characterized by a high mutational burden and microsatellite instability-high (MSI-H) tumors. Immunology of LS-associated CRC (LS-CRC) is unique, with significant implications for treatment. Despite well-established knowledge of LS immunology, immunotherapy dose and treatment response can vary significantly based on local tumor immunity and specific germline pathogenic variant of LS genes. This variability necessitates tailored surveillance strategies and new personalised immunotherapy approaches for LS patients. LS-CRC often benefits from immunotherapy due to the distinct tumor microenvironment (TME) and the variety of tumor infiltrating lymphocytes (TILs). This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images (WSIs) that accounts for the distinct TME of LS-CRC. By emphasizing the necessity of personalized medicine in hereditary cancer syndromes, the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 3-7"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link","authors":"Alanoud Abdulla ,&nbsp;Hana Q. Sadida ,&nbsp;Jayakumar Jerobin ,&nbsp;Imadeldin Elfaki ,&nbsp;Rashid Mir ,&nbsp;Sameer Mirza ,&nbsp;Mayank Singh ,&nbsp;Muzafar A. Macha ,&nbsp;Shahab Uddin ,&nbsp;Khalid Fakhro ,&nbsp;Ajaz A. Bhat ,&nbsp;Ammira S. Al-Shabeeb Akil","doi":"10.1016/j.jncc.2024.11.001","DOIUrl":"10.1016/j.jncc.2024.11.001","url":null,"abstract":"<div><div>Obesity, a global health concern, is associated with severe health issues like type 2 diabetes, heart disease, and respiratory complications. It also increases the risk of various cancers, including melanoma, endometrial, prostate, pancreatic, esophageal adenocarcinoma, colorectal carcinoma, renal adenocarcinoma, and pre-and post-menopausal breast cancer. Obesity-induced cellular changes, such as impaired CD8⁺ T cell function, dyslipidemia, hypercholesterolemia, insulin resistance, mild hyperglycemia, and fluctuating levels of leptin, resistin, adiponectin, and IL-6, contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes. Adipocytes release leptin, a pro-inflammatory substance that stimulates cancer cell proliferation, inflammation, and invasion, altering the tumor cell metabolic pathway. Adiponectin, an insulin-sensitizing adipokine, is typically downregulated in obese individuals. It has antiproliferative, proapoptotic, and antiangiogenic properties, making it a potential cancer treatment. This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer, drawing on an extensive, though non-systematic, survey of the recent literature. This approach allows us to integrate and synthesize findings from various studies, offering a cohesive perspective on emerging themes and potential therapeutic targets. The review explores the metabolic disturbances, cellular alterations, inflammatory responses, and shifts in the tumor microenvironment that contribute to the obesity-cancer link. Finally, it discusses potential therapeutic strategies aimed at disrupting these connections, offering valuable insights into future research directions and the development of targeted interventions.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 8-27"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese expert consensus on flow cytometric detection of hematological malignant cells in tissue samples","authors":"Zailin Yang ,&nbsp;Xia Mao ,&nbsp;Mingxia Zhu ,&nbsp;Shuang Chen ,&nbsp;Zifen Gao ,&nbsp;Tingting Jiang ,&nbsp;Yu Peng ,&nbsp;Fanggang Ren ,&nbsp;Huijun Wang ,&nbsp;Lili Wang ,&nbsp;Suigui Wan ,&nbsp;Xiangqin Weng ,&nbsp;Chunyan Wang ,&nbsp;Yujie Wu ,&nbsp;Yazhe Wang ,&nbsp;Yonggang Xu ,&nbsp;Jie Zhu ,&nbsp;Mingqing Zhu ,&nbsp;Yaping Zhai ,&nbsp;Hongmei Jing ,&nbsp;Yanrong Liu","doi":"10.1016/j.jncc.2024.11.003","DOIUrl":"10.1016/j.jncc.2024.11.003","url":null,"abstract":"<div><div>Flow cytometry (FCM), characterized by its simplicity, rapid processing, multiparameter analysis, and high sensitivity, is widely used in the diagnosis, treatment, and prognosis of hematological malignancies. FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers, but also enables the detection of solid tumors. Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities, such as in fine-needle biopsy samples. This attribute not only addresses the challenge posed by small sample sizes, but also boosts the sensitivity of tumor cell detection. The significance of FCM in clinical and pathological applications continues to grow. To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process, experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus. This consensus was formulated based on current literature and clinical practices of all experts across clinical, laboratory, and pathological fields in China. It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples, including report content, interpretation, quality control, and key considerations. Additionally, it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests, particularly in cases with limited sample sizes.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 28-37"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatments of transarterial chemoembolization (TACE), stereotactic body radiotherapy (SBRT) and immunotherapy reshape the systemic tumor immune environment (STIE) in patients with unresectable hepatocellular carcinoma","authors":"Cai-Ning Zhao ,&nbsp;Chi-Leung Chiang ,&nbsp;Wan-Hang Keith Chiu ,&nbsp;Sik-Kwan Kenneth Chan ,&nbsp;Chun-Bong James Li ,&nbsp;Wei-Wei Chen ,&nbsp;Dan-Yang Zheng ,&nbsp;Wen-Qi Chen ,&nbsp;Ren Ji ,&nbsp;Chung-Mau Lo ,&nbsp;Salma K. Jabbour ,&nbsp;Chi-Yan Albert Chan ,&nbsp;Feng-Ming (Spring) Kong","doi":"10.1016/j.jncc.2024.06.007","DOIUrl":"10.1016/j.jncc.2024.06.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The role of systemic tumor immune environment (STIE) is unclear in hepatocellular carcinoma (HCC). This study aimed to exam the cells in the STIE, their changes after transarterial chemoembolisation (TACE), stereotactic body radiotherapy (SBRT), and immunotherapy (IO) and explore their significance in the treatment response of patients with unresectable HCC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This is a prospective biomarker study of patients with unresectable HCC. The treatment was sequential TACE, SBRT (27.5–40 Gy/5 fractions), and IO. The treatment response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) by magnetic resonance imaging (MRI) after 6 months of treatment. Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts, including leukocytes, lymphocytes, neutrophils, monocytes, eosinophils, basophils, and platelets. Peripheral blood samples were collected at baseline and after TACE, SBRT, and IO for T-lymphocyte subtyping by flow cytometry. Generalized estimation equation was employed for longitudinal analyses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 35 patients with unresectable HCC were enrolled: 23 patients in the exploratory cohort and 12 in the validation cohort. STIE circulating cells, especially lymphocytes, were heterogenous at baseline and changed differentially after TACE, SBRT, and IO in both cohorts. SBRT caused the greatest reduction of 0.7 × 10&lt;sup&gt;9&lt;/sup&gt;/L (95 % CI: 0.3 × 10&lt;sup&gt;9&lt;/sup&gt;/L–1.0 × 10&lt;sup&gt;9&lt;/sup&gt;/L, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) in lymphocytes; less reduction was associated with significantly better treatment response. The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4&lt;sup&gt;+&lt;/sup&gt; T cells (&lt;em&gt;P&lt;/em&gt; = 0.010), type 1 T helper (Th1) cells (&lt;em&gt;P&lt;/em&gt; = 0.007), and Th1/Th17 ratios (&lt;em&gt;P&lt;/em&gt; = 0.001) were significantly higher in responders, while regulatory T (Treg) cells (&lt;em&gt;P&lt;/em&gt; = 0.002), Th17 cells (&lt;em&gt;P&lt;/em&gt; = 0.047), and Th2/Th1 ratios (&lt;em&gt;P&lt;/em&gt; = 0.028) were significantly higher in non-responders. After treatment with TACE, SBRT and IO, T-lymphocyte lineage also changed differentially. More reductions were observed in CD25&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells and CD127&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells after SBRT in non-responders, while increases in natural killer T (NKT) cells after SBRT (10.4% vs. 3.4 %, &lt;em&gt;P&lt;/em&gt; = 0.001) and increases in the lymphocyte counts were noted during IO in responders.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;STIE cells are significant for treatment response, can be reshaped differentially after TACE, SBRT, and IO. The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells, CD127&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells, and NKT cells, which also have significant effects on the ultimate treatment response after TACE-SBRT-IO (ClinicalTrails.gov identifier: GCOG0001/NC","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 38-49"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}