Tianzi Wang, Chang Liu, Xuefeng Hu, Ning Yang, Chen Qiu
{"title":"Senescent macrophages in cancer: roles in tumor progression and treatment opportunities.","authors":"Tianzi Wang, Chang Liu, Xuefeng Hu, Ning Yang, Chen Qiu","doi":"10.20892/j.issn.2095-3941.2024.0589","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0589","url":null,"abstract":"<p><p>Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores the multifaceted roles of macrophage senescence in cancer, and establishes links between senescent macrophages and tumor progression from multiple perspectives, on the basis of the first comprehensive analysis of the molecular mechanisms and pathways involved. By systematically examining the diverse changes in senescent macrophages, this review integrates and analyzes their effects on tumors, thus offering a comprehensive and novel theoretical foundation, and practical insights for cancer treatment. Notably, by integrating current molecular research and therapeutic advancements, we summarize novel therapeutic strategies targeting senescent macrophages, including senolytics, senescence modulators, and cutting-edge immunotherapies, thereby highlighting the potential of senescent macrophages as a therapeutic target and introducing new opportunities for cancer treatment.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977475","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":"The treatment of breast cancer in the era of precision medicine.","authors":"Jingwen Bai, Yiyang Gao, Guojun Zhang","doi":"10.20892/j.issn.2095-3941.2024.0510","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0510","url":null,"abstract":"<p><p>The management of breast cancer, one of the most common and heterogeneous malignancies, has transformed with the advent of precision medicine. This review explores current developments in genetic profiling, molecular diagnostics, and targeted therapies that have revolutionized breast cancer treatment. Key innovations, such as cyclin-dependent kinases 4/6 (CDK4/6) inhibitors, antibody-drug conjugates (ADCs), and immune checkpoint inhibitors (ICIs), have improved outcomes for hormone receptor-positive (HR+), HER2-positive (HER2+), and triple-negative breast cancer (TNBC) subtypes remarkably. Additionally, emerging treatments, such as PI3K inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, and mRNA-based therapies, offer new avenues for targeting specific genetic mutations and improving treatment response, particularly in difficult-to-treat breast cancer subtypes. The integration of liquid biopsy technologies provides a non-invasive approach for real-time monitoring of tumor evolution and treatment response, thus enabling dynamic adjustments to therapy. Molecular imaging and artificial intelligence (AI) are increasingly crucial in enhancing diagnostic precision, personalizing treatment plans, and predicting therapeutic outcomes. As precision medicine continues to evolve, it has the potential to significantly improve survival rates, decrease recurrence, and enhance quality of life for patients with breast cancer. By combining cutting-edge diagnostics, personalized therapies, and emerging treatments, precision medicine can transform breast cancer care by offering more effective, individualized, and less invasive treatment options.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954749","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":"Cancer-derived exosomal circTMEM56 enhances the efficacy of HCC radiotherapy through the miR-136-5p/STING axis.","authors":"Li Yuan, Yue Wang, Junjie Cheng, Shilin Lin, Aying Ma, Kunchao Li, Yiming Zheng, Zhaochong Zeng, Aiwu Ke, Chao Gao, Shisuo Du","doi":"10.20892/j.issn.2095-3941.2024.0544","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0544","url":null,"abstract":"<p><strong>Objective: </strong>Although the role of circular RNAs (circRNAs) in tumor progression and immune regulation is well-known, the specific circRNA molecules that mediate immune responses after radiotherapy (RT) and the underlying mechanisms have not been identified.</p><p><strong>Methods: </strong>Cytometry with time-of-flight (CyTOF) was used to analyze blood samples from patients with liver cancer exhibiting abscopal effects (AEs) after stereotactic body radiotherapy (SBRT) to quantify the number of dendritic cells (DCs) and CD8<sup>+</sup> T cells and interferon-beta (IFN-β) level. circTMEM56 and IFN-β levels were measured in 76 patients with liver cancer using qPCR and ELISA. Immunohistochemistry validated circTMEM56 and CD141 staining in tissues. The interaction between circTMEM56, miR-136-5p, and STING, as well as the impact on anti-tumor immunity, was verified using circTMEM56-specific probes, dual-luciferase activity assays, proteomics analysis, and western blot analysis.</p><p><strong>Results: </strong>The role of circTMEM56 in enhancing anti-tumor immunity and response to RT in hepatocellular carcinoma (HCC) was determined. Higher circTMEM56 levels were linked to an improved RT response and better clinical outcomes in patients with HCC. circTMEM56 enhanced cGAS-STING signaling, increased the number of tumor-infiltrating CD8<sup>+</sup> T cells, and elevated the serum IFN-β levels. Moreover, circTMEM56 administration significantly boosted the response to RT in tumors with low circTMEM56 expression.</p><p><strong>Conclusions: </strong>High circTMEM56 expression in HCC modulates the distant effects of HCC RT by activating the cGAS-STING pathway to reshape the tumor microenvironment. This study provides a new approach to improve RT efficacy for HCC.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977134","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":"Plasma <i>L</i>-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization study.","authors":"Mengyuan Wang, Zhouyi Yin, Hengmin Xu, Zongchao Liu, Sha Huang, Wenhui Wu, Yang Zhang, Tong Zhou, Weicheng You, Kaifeng Pan, Wenqing Li","doi":"10.20892/j.issn.2095-3941.2024.0523","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0523","url":null,"abstract":"<p><strong>Objective: </strong>Based on multistage metabolomic profiling and Mendelian randomization analyses, the current study identified plasma metabolites that predicted the risk of developing gastric cancer (GC) and determined whether key metabolite levels modified the GC primary prevention effects.</p><p><strong>Methods: </strong>Plasma metabolites associated with GC risk were identified through a case-control study. Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial (SIT), a nested case-control study of the Mass Intervention Trial in Linqu, Shandong province (MITS), China, the UK Biobank, and the FinnGen project.</p><p><strong>Results: </strong>A higher genetic risk score for plasma <i>L</i>-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population (SIT: HR = 1.26 per 1 <i>SD</i> change, 95% CI: 1.07-1.49; MITS: HR = 1.07, 95% CI: 1.00-1.14) and an increased gastric adenocarcinoma risk in FinnGen (OR = 1.68, 95% CI: 1.16-2.45). Genetically predicted plasma <i>L</i>-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of <i>Helicobacter pylori</i> eradication notably observed among individuals within the top quartile of <i>L</i>-aspartic acid level (<i>P</i>-interaction = 0.098) and the beneficial effect of garlic supplementation only for those within the lowest quartile of <i>L</i>-aspartic acid level (<i>P</i>-interaction = 0.02).</p><p><strong>Conclusions: </strong>Elevated plasma <i>L</i>-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention. Further studies from other populations are warranted to validate the modification effect of plasma <i>L</i>-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977842","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}
Tianshu Yu, Xianhuo Wang, Ou Bai, Huilai Zhang, Wenbin Qian
{"title":"Advances in strategies to improve the immunotherapeutic efficacy of chimeric antigen receptor-T cell therapy for lymphoma.","authors":"Tianshu Yu, Xianhuo Wang, Ou Bai, Huilai Zhang, Wenbin Qian","doi":"10.20892/j.issn.2095-3941.2024.0538","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0538","url":null,"abstract":"<p><p>Chimeric antigen receptor-T (CAR-T) cell therapy is a precise immunotherapy for lymphoma. However, its long-term efficacy faces many challenges related to tumor cell heterogeneity, interference from immunosuppressive microenvironments, CAR-T cell exhaustion, and unmanageable adverse events. Diverse modifications have been introduced into conventional CAR-T cells to overcome these obstacles; examples include addition of recognition sites to prevent immune escape, coupling of cytokine domains to enhance killing ability, blocking of immune checkpoint signals to resist tumor microenvironments, and inclusion of suicide systems or safety switches to improve safety and flexibility. With increasing understanding of the importance of metabolism and epigenetics in cancer and cytotherapy, glycolysis, methylation, and acetylation have become crucial CAR-T cell therapeutic targets. Universal and <i>in situ</i> CAR-T cells are also expected to be used in clinical applications, thus providing hope to patients with relapsed/refractory lymphomas.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984746","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":"Neoepitope BTLA<sup>P267L</sup>-specific TCR-T cell immunotherapy unlocks precision treatment for hepatocellular carcinoma.","authors":"Fang Liu, Hua Chen, Suxin Wu, Chenlu Zhu, Mingji Zhang, Wei Rui, Dong Zhou, Yang Wang, Xin Lin, Xueqiang Zhao, Yunbin Ye","doi":"10.20892/j.issn.2095-3941.2024.0434","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0434","url":null,"abstract":"<p><strong>Objective: </strong>The high heterogeneity of hepatocellular carcinoma (HCC) renders traditional therapies unable to effectively activate the patient's immune system to combat tumors. Patients with advanced HCC and T cell functional deficiencies may benefit more from cellular immunotherapy, especially tumor neoepitope-targeted T cell receptor (TCR)-T cells. Neoepitopes with strong immunogenicity provide precise targets for HCC, further enhancing the efficacy of cellular immunotherapy.</p><p><strong>Methods: </strong>A scalable workflow for identifying neoepitopes from 7 HLA-A*02:01-restricted patients with HCC was established based on whole exome sequencing and bioinformatics analyses, followed by identification of neoepitope-specific TCRs through tetramer-based screening and single-cell TCR cloning technology, which were further validated in the JC4 cell model. The cytotoxicity of CD8<sup>+</sup> TCR-T cells was evaluated in neoepitope-positive tumor cell lines or NCG mice.</p><p><strong>Results: </strong>Ten specific neoepitopes were identified, among which neoepitope B and T lymphocyte attenuator<sup>P267L</sup> [BTLA<sup>P267L</sup> (SLNHSVIGL)] exhibited advantageous properties as a potential tumor target. Three TCRs (85-3, 126-5, and 52-3) were confirmed to specifically recognize the neoepitope BTLA<sup>P267L</sup>, while no cross-recognition of irrelevant or wild-type epitopes was observed. Activated BTLA<sup>P267L</sup>-specific CD8<sup>+</sup> TCR-T cells released extensive perforin, granzyme B, IFN-γ, and TNF-α <i>in vitro</i>, thereby inducing strong cytotoxic effects against BTLA<sup>P267L</sup>-positive T2 or HCC cell lines. BTLA<sup>P267L</sup>-specific CD8<sup>+</sup> TCR-T cells mediated robust tumor regression due to long-lasting survival and released perforin without causing significant cytotoxic effects on normal organs in murine experiments.</p><p><strong>Conclusions: </strong>This preclinical study demonstrated the beneficial effects of neoepitope BTLA<sup>P267L</sup>-specific TCR-T cell immunotherapy, unlocking a novel strategy for personalized precision therapy in HCC.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954849","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":"Expert consensus on the diagnosis and treatment of non-small cell lung cancer with MET alteration.","authors":"Huijing Feng, Yang Xia, Wenxian Wang, Chunwei Xu, Qian Wang, Zhengbo Song, Ziming Li, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Anwen Liu, Wen Li, Ping Zhan, Hongbing Liu, Tangfeng Lyu, Liyun Miao, Lingfeng Min, Gen Lin, Long Huang, Jingping Yuan, Zhansheng Jiang, Xingxiang Pu, Chuangzhou Rao, Dongqing Lyu, Zongyang Yu, Xiaoyan Li, Chuanhao Tang, Chengzhi Zhou, Qi Mei, Hui Guo, Qian Chu, Rui Meng, Xuewen Liu, Jingxun Wu, Jin Zhou, Zhengfei Zhu, Weiwei Pan, Fei Pang, Meizhen Hu, Kai Wang, Fan Wu, Bingwei Xu, Ling Xu, Liping Wang, Youcai Zhu, Jisheng Li, Yanru Xie, Xinqing Lin, Jing Cai, Lin Wang, Yingying Du, Wang Yao, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jing Kang, Jiatao Zhang, Chao Zhang, Wenbin Gao, Jianhui Huang, Yinbin Zhang, Pingli Sun, Hong Wang, Mingxiang Ye, Dong Wang, Zhaofeng Wang, Yue Hao, Zheng Wang, Bing Wan, Donglai Lyu, Xiaodong Jiao, Lin Shi, Gang Lan, Shengjie Yang, Yanhong Shang, Yina Wang, Bihui Li, Gang Jin, Kang Zheng, Jun Ma, Wenfeng Li, Zhang Zhang, Zhongwu Li, Yuan Li, Zhefeng Liu, Xuelei Ma, Nong Yang, Lin Wu, Qiming Wang, Guansong Wang, Zhuan Hong, Jiandong Wang, Meiyu Fang, Yong Fang, Xixu Zhu, Yi Shen, Ke Wang, Xiubao Ren, Yiping Zhang, Shenglin Ma, Junping Zhang, Yong Song, Wenfeng Fang, Yuanzhi Lu","doi":"10.20892/j.issn.2095-3941.2024.0503","DOIUrl":"10.20892/j.issn.2095-3941.2024.0503","url":null,"abstract":"<p><p>Alterations in the mesenchymal-epithelial transition factor (<i>MET</i>) gene are critical drivers of non-small cell lung cancer (NSCLC). In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients. These alterations include <i>MET</i> exon 14 skipping mutations (<i>MET</i> exon 14 skipping), <i>MET</i> gene amplifications, <i>MET</i> point mutations (primarily kinase domain mutations), and MET protein overexpression. Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes. The East China Lung Cancer Group, Youth Committee (ECLUNG YOUNG, Yangtze River Delta Lung Cancer Cooperation Group) has synthesized insights from China's innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations. This consensus addresses key areas, such as optimal testing timing, testing methods, testing strategies, quality control measures, and treatment approaches. By offering standardized recommendations, this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":"22 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810561","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}
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