Cancer letters最新文献_第7页

A single-cell map of patients with non-small cell lung cancer harboring rare-driver mutations after anti-PD-1 treatment

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-26 DOI: 10.1016/j.canlet.2025.217595

Rui Fu , Chao Zhang , Meng-Meng Song , Xuan Gao , Fang Li , Miao Cai , Ben-Yuan Jiang , Xue-Ning Yang , Yi-Long Wu , Wen-Zhao Zhong

{"title":"A single-cell map of patients with non-small cell lung cancer harboring rare-driver mutations after anti-PD-1 treatment","authors":"Rui Fu , Chao Zhang , Meng-Meng Song , Xuan Gao , Fang Li , Miao Cai , Ben-Yuan Jiang , Xue-Ning Yang , Yi-Long Wu , Wen-Zhao Zhong","doi":"10.1016/j.canlet.2025.217595","DOIUrl":"10.1016/j.canlet.2025.217595","url":null,"abstract":"<div><div>The effects of the tumor microenvironment the therapeutic efficacy of combining chemotherapy with checkpoint inhibitors in patients with lung cancer harboring rare -driver mutations remain unclear. We utilized single-cell RNA- and T-cell receptor (TCR) -sequencing to explore the immune and stromal cell profiles of 12 tumors and five tumor-adjacent tissues in seven patients with non-small cell lung cancer (NSCLCs) with rare -driver mutations treated with anti-PD-1 agents combined with chemotherapy. A class of highly expanded T -cells, known as GZMK + CD8<sup>+</sup> effector memory T cells (GZMK + CD8+Tem), was enriched in both responsive tumors with and without rare driver mutations, suggesting similar anti-tumor immune mechanisms in both cohorts and that high levels of GZMK + CD8+Tem might be associated with effective responses to combination therapy. Non-responsive tumors exhibited a highly immunosuppressive M2-phenotype with enriched macrophages and monocytes. In non-major pathological response tumors, tumor cells interacted with alveolar and M0 macrophages via LAMC2-(ITGA6+ITGB1), possibly leading to M2 polarization. <em>OAS1</em> was specifically expressed in CHIT1+ and FABP4+ macrophages and promoted macrophage polarization. These findings suggest that combination therapy reprogramed alveolar and M0-like macrophages to a pro-tumor phenotype, creating an immunosuppressive tumor microenvironment that resisted anti-PD1 therapy. In conclusion, GZMK + CD8+Tem is crucial for effective responses, whereas myeloid cells contribute to the immunosuppressive effects in anti-PD-1 therapies for NSCLCs with rare-driver mutations.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217595"},"PeriodicalIF":9.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing the antitumor effect of MUC16 CART cells in ovarian cancer: The potential of oncolytic adenovirus

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-25 DOI: 10.1016/j.canlet.2025.217588

Qiuman Wang , Wanchuan Liu , Yuanchun Fan , Shihao Liu , Rongrong Li , Shi Yan , Kun Song , Hui Zhang , Cunzhong Yuan

引用次数: 0

Neural-cancer crosstalk: Reciprocal molecular circuits driving gastric tumorigenesis and emerging therapeutic opportunities

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-25 DOI: 10.1016/j.canlet.2025.217589

Ning Li , Huyun Tong , Wenqing Hou , Qin Liu , Fei Xiang , Jian-wu Zhu , Sen-lin Xu , Zongsheng He , Bin Wang

{"title":"Neural-cancer crosstalk: Reciprocal molecular circuits driving gastric tumorigenesis and emerging therapeutic opportunities","authors":"Ning Li , Huyun Tong , Wenqing Hou , Qin Liu , Fei Xiang , Jian-wu Zhu , Sen-lin Xu , Zongsheng He , Bin Wang","doi":"10.1016/j.canlet.2025.217589","DOIUrl":"10.1016/j.canlet.2025.217589","url":null,"abstract":"<div><div>The nervous system plays an important role in regulating physiological functions of the stomach, and its abnormal activity often impairs gastric homeostasis. In response to constant exposure to oncogenic stimuli that leads to gastric tumorigenesis, the neural system becomes an essential component of the tumor microenvironment via perineural infiltration, <em>de novo</em> neurogenesis, and axonogenesis, thereby driving cancer initiation and progression. In this review, we highlight emerging discoveries related to neural-cancer crosstalk and discuss how the nervous system is remodeled by tumor cells including neural components and modulators (including neurotransmitters and neuropeptides). Moreover, we provide a systematic analysis of neural control of the cellular hallmarks of cancer. Finally, we propose how the molecular circuits of neural-cancer crosstalk could be exploited as potential targets for novel anti-cancer treatment, providing new insights into a new modality of neural-based cancer therapeutic strategies.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217589"},"PeriodicalIF":9.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “B cell CLL/lymphoma 6 member B inhibits hepatocellular carcinoma metastases in vitro and in mice” [Cancer Lett. 355 (2014) 192–200]

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-25 DOI: 10.1016/j.canlet.2025.217564

Jia Wang , Ling Dong , Lixia Xu , Eagle SH. Chu , Yangchao Chen , Jiayun Shen , Xiaoxing Li , Chi Chun Wong , Joseph JY. Sung , Jun Yu

引用次数: 0

SQLE-catalyzed squalene metabolism promotes mitochondrial biogenesis and tumor development in K-ras-driven cancer

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-25 DOI: 10.1016/j.canlet.2025.217586

Junchen Pan , Rui Liu , Wenhua Lu , Hongyu Peng , Jing Yang , Qianrui Zhang , Tiantian Yu , Bitao Huo , Xiaoying Wei , Haixi Liang , Lin Zhou , Yameng Sun , Yumin Hu , Shijun Wen , Jie Fu , Paul J. Chiao , Xiaojun Xia , Jinyun Liu , Peng Huang

{"title":"SQLE-catalyzed squalene metabolism promotes mitochondrial biogenesis and tumor development in K-ras-driven cancer","authors":"Junchen Pan , Rui Liu , Wenhua Lu , Hongyu Peng , Jing Yang , Qianrui Zhang , Tiantian Yu , Bitao Huo , Xiaoying Wei , Haixi Liang , Lin Zhou , Yameng Sun , Yumin Hu , Shijun Wen , Jie Fu , Paul J. Chiao , Xiaojun Xia , Jinyun Liu , Peng Huang","doi":"10.1016/j.canlet.2025.217586","DOIUrl":"10.1016/j.canlet.2025.217586","url":null,"abstract":"<div><div>It is well known that activation of oncogenic K-ras alone is insufficient to drive tumor development and that additional factors are needed for full malignant transformation, but the metabolic pathways and regulatory mechanisms that facilitate K-ras-driven cancer development remain to be characterized. Here we show that SQLE, a key enzyme in cholesterol synthesis, is upregulated in K-ras-driven cancer and its high expression is correlated with poor clinical outcome. K-ras regulates SQLE expression in a biphasic manner through reactive oxygen species and MYC signaling. Surprisingly, the pro-oncogenic role of SQLE is not mediated by promoting cholesterol synthesis, but by metabolic removal of squalene and thus mitigating its suppressive effect on the PGC-1α-mediated mitochondrial biogenesis and metabolism. Genetic silencing of SQLE in pancreatic cancer cells causes an accumulation of cellular squalene, which binds to Sp1 protein and causes a formation of a tight Sp1-TFAP2E promoter DNA complex with a highly negative binding score. This aberrant squalene/Sp1/TFAP2E promoter complex hinders the expression of TFAP2E and its downstream molecule PGC-1α, leading to suppression of mitochondrial metabolism and an almost complete inhibition of tumor formation <em>in vivo</em>. Importantly, administration of pharmacological squalene to mice bearing pancreatic cancer xenografts could significantly inhibit tumor growth. Our study has revealed a previously unrecognized role of SQLE in regulating gene expression and mitochondrial metabolism to facilitate K-ras-driven cancer development, and identified SQLE as a novel therapeutic target for potential treatment of pancreatic cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217586"},"PeriodicalIF":9.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the role of liquid-liquid phase separation in sarcoma: Implications for pathogenesis and treatment

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-23 DOI: 10.1016/j.canlet.2025.217585

Zehao Cheng , Hua Wang , Yibo Zhang , Bolin Ren , Zheng Fu , Zhihong Li , Chao Tu

{"title":"Deciphering the role of liquid-liquid phase separation in sarcoma: Implications for pathogenesis and treatment","authors":"Zehao Cheng , Hua Wang , Yibo Zhang , Bolin Ren , Zheng Fu , Zhihong Li , Chao Tu","doi":"10.1016/j.canlet.2025.217585","DOIUrl":"10.1016/j.canlet.2025.217585","url":null,"abstract":"<div><div>Liquid-liquid phase separation (LLPS) is a significant reversible and dynamic process in organisms. Cells form droplets that are distinct from membrane-bound cell organelles by phase separation to keep biochemical processes in order. Nevertheless, the pathological state of LLPS contributes to the progression of a variety of tumor-related pathogenic issues. Sarcoma is one kind of highly malignant tumor characterized by aggressive metastatic potential and resistance to conventional therapeutic agents. Despite the significant clinical relevance, research on phase separation in sarcomas currently faces several major challenges. These include the limited availability of sarcoma samples, insufficient attention from the research community, and the complex genetic heterogeneity of sarcomas. Recently, emerging evidence have elaborated the specific effects and pathways of phase separation on different sarcoma subtypes, including the effect of sarcoma fusion proteins and other physicochemical factors on phase separation. This review aims to summarize the multiple roles of phase separation in sarcoma and novel molecular inhibitors that target phase separation. These insights will broaden the understanding of the mechanisms concerning sarcoma and offer new perspectives for future therapeutic strategies.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217585"},"PeriodicalIF":9.1,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct immunophenotypic profiles and neutrophil heterogeneity in colorectal cancer

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-22 DOI: 10.1016/j.canlet.2025.217570

Minghua Bai , Yuzhao Jin , Zihao Jin , Yuhao Xie , Jinggang Chen , Qingping Zhong , Zhenbo Wang , Qian Zhang , Yibo Cai , FangYa Qun , Nitta Yuki , Cheng Xin , Xiaohui Shen , Ji Zhu

{"title":"Distinct immunophenotypic profiles and neutrophil heterogeneity in colorectal cancer","authors":"Minghua Bai , Yuzhao Jin , Zihao Jin , Yuhao Xie , Jinggang Chen , Qingping Zhong , Zhenbo Wang , Qian Zhang , Yibo Cai , FangYa Qun , Nitta Yuki , Cheng Xin , Xiaohui Shen , Ji Zhu","doi":"10.1016/j.canlet.2025.217570","DOIUrl":"10.1016/j.canlet.2025.217570","url":null,"abstract":"<div><div>Colorectal cancer (CRC) exhibits significant molecular and immunological heterogeneity. Neutrophil infiltration patterns play a crucial yet poorly understood role in tumor progression and patient outcomes. This study presents a comprehensive single-cell atlas of the CRC tumor microenvironment (TME), integrating transcriptomic data from 388,511 cells across 98 samples from 63 patients. Employing advanced computational methods, we stratified patients based on their immune cell infiltration profiles, revealing distinct immunophenotypes with potential therapeutic implications. Our analysis focused on tissue-resident neutrophils (TRNs) and uncovered previously uncharacterized subpopulations with diverse functional states. Trajectory inference analysis revealed a dynamic differentiation path from normal-associated neutrophils to tumor-associated neutrophils, highlighting the remarkable plasticity of these cells within the tumor environment. By integrating single-cell data with bulk transcriptomic and clinical information, we identified specific neutrophil-derived gene signatures associated with poor prognosis in CRC, suggesting their potential as novel prognostic biomarkers. This study not only provides unprecedented insights into neutrophil heterogeneity in CRC but also identifies potential targets for immunomodulatory therapies. Our findings lay the groundwork for developing more nuanced, personalized immunotherapeutic strategies for CRC, potentially improving treatment efficacy for patients who currently show a limited response to existing immunotherapies.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217570"},"PeriodicalIF":9.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PRTN3 promotes IL33/Treg-mediated tumor immunosuppression by enhancing the M2 polarization of tumor-associated macrophages in lung adenocarcinoma

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-22 DOI: 10.1016/j.canlet.2025.217584

Jiayu Jiang , Huilin Chen , Chunxing Zhao , Tong Li , Chen Zhang , Lingyu Ma , Huifang Su , Lei Ma , Zhaojun Duan , Qin Si , Tsung-Hsien Chuang , Chong Chen , Yunping Luo

{"title":"PRTN3 promotes IL33/Treg-mediated tumor immunosuppression by enhancing the M2 polarization of tumor-associated macrophages in lung adenocarcinoma","authors":"Jiayu Jiang , Huilin Chen , Chunxing Zhao , Tong Li , Chen Zhang , Lingyu Ma , Huifang Su , Lei Ma , Zhaojun Duan , Qin Si , Tsung-Hsien Chuang , Chong Chen , Yunping Luo","doi":"10.1016/j.canlet.2025.217584","DOIUrl":"10.1016/j.canlet.2025.217584","url":null,"abstract":"<div><div>The immunosuppressive tumor microenvironment (TME) shaped by tumor-associated macrophages (TAMs) is essential for lung adenocarcinoma (LUAD) immune tolerance and tumor progression. Here, we first reported that proteinase 3 (PRTN3) promoted the alternative activation (M2) of TAMs and enhanced IL33/regulatory T cells (Tregs)-mediated tumor immunosuppression in LUAD. Firstly, clinical analysis revealed PRTN3 was highly expressed in TAMs and correlated with the tumor progression and poor prognosis in LUAD patients. Meanwhile, by using the myeloid cells-specific <em>Prtn3</em>-knockout mouse model, we demonstrated <em>Prtn3</em> deficiency in macrophages remolded the immunosuppressive TME and suppressed tumor growth. The mechanism studies uncovered a novel signaling pathway that PRTN3 up-regulated IL33 expression in TAMs by suppressing AKT-mediated ubiquitinated degradation of FOXO1, which subsequently activated <em>Il33</em> transcription. Furthermore, lack of PRTN3 or FOXO1 in macrophages greatly restrained IL33-induced Treg differentiation. Importantly, selective knockout of <em>Prtn3</em> in macrophages significantly enhanced the antitumor effect of anti-PD1 therapy in the mouse model of LUAD. Thus, our work demonstrated that PRTN3 in macrophages, served as a key immunoregulator, contributed to impede the antitumor immune response through reinforcing the TAMs/Tregs crosstalk, which provided valuable insights to improve the immunotherapeutic effect by functional remodeling of TAMs to alleviate immunosuppression in LUAD.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217584"},"PeriodicalIF":9.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurturin-Induced Activation of GFRA2-RET Axis Potentiates Pancreatic Cancer Glycolysis via Phosphorylated Hexokinase 2.

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-21 DOI: 10.1016/j.canlet.2025.217583

Ran Cui, Gaoming Wang, Fuguo Liu, Yongkun Wang, Zinan Zhao, Muladili Mutailipu, Huiling Mu, Xiaohua Jiang, Wenjun Le, Ludi Yang, Bo Chen

{"title":"Neurturin-Induced Activation of GFRA2-RET Axis Potentiates Pancreatic Cancer Glycolysis via Phosphorylated Hexokinase 2.","authors":"Ran Cui, Gaoming Wang, Fuguo Liu, Yongkun Wang, Zinan Zhao, Muladili Mutailipu, Huiling Mu, Xiaohua Jiang, Wenjun Le, Ludi Yang, Bo Chen","doi":"10.1016/j.canlet.2025.217583","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217583","url":null,"abstract":"<p><p>Pancreatic cancer, characterized by its insidious onset, high invasiveness, resistance to chemotherapy, and a grim prognosis, with a five-year survival rate hovering below 10%. The identification of novel therapeutic targets addressing tumor progression is therefore critically important. While perineural invasion (PNI) is recognized as a pathological hallmark and key driver of pancreatic cancer progression, its role in metabolic reprogramming of malignant cells has not been fully elucidated. Using integrated metabolomics approaches, we found perineural invasion in pancreatic cancer significantly enhancing glycolytic flux of pancreatic cancer. Our data delineate a neuroendocrine-paracrine signaling axis in which neurturin secreted by neuronal cells binds to the GFRA2 receptor on pancreatic cancer cells, inducing RET kinase recruitment and subsequent heterodimer assembly. This receptor tyrosine kinase complex phosphorylates hexokinase 2 (HK2) at the evolutionarily conserved Ser122 residue, augmenting its hexokinase activity, ultimately driving aerobic glycolysis flux and fueling pancreatic cancer growth. In vivo experiments corroborate our findings, revealing that neurturin blockade effectively halts pancreatic cancer progression and synergizes with RET inhibitors. Our research underscores neurturin as a promising therapeutic target for the treatment of pancreatic cancer.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217583"},"PeriodicalIF":9.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer [Cancer Lett. 379 (2016) 1–11]

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-20 DOI: 10.1016/j.canlet.2025.217562

Huai-Qiang Ju , Zhuo-Nan Zhuang , Hao Li , Tian Tian , Yun-Xin Lu , Xiao-Qiang Fan , Hai-Jun Zhou , Hai-Yu Mo , Hui Sheng , Paul J. Chiao , Rui-Hua Xu

引用次数: 0