Cancer Science最新文献_第4页

Transferrin Receptor Promotes Endometrial Cancer Proliferation by Activating the Iron-Dependent PI3K/AKT/mTOR Signaling Pathway 转铁蛋白受体通过激活铁依赖性 PI3K/AKT/mTOR 信号通路促进子宫内膜癌增殖

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-01 DOI: 10.1111/cas.70015

Yufei Yang, Ying Ning, Yu Chen, Tian Tian, Xinyan Gao, Yan Kong, Ke Lei, Zhumei Cui

{"title":"Transferrin Receptor Promotes Endometrial Cancer Proliferation by Activating the Iron-Dependent PI3K/AKT/mTOR Signaling Pathway","authors":"Yufei Yang, Ying Ning, Yu Chen, Tian Tian, Xinyan Gao, Yan Kong, Ke Lei, Zhumei Cui","doi":"10.1111/cas.70015","DOIUrl":"10.1111/cas.70015","url":null,"abstract":"Aberrant iron metabolism is frequently observed in cancers, including endometrial cancer (EC). However, the role of transferrin receptor (TFRC), a key regulator of iron metabolism, remains unclear in endometrial cancer. We found transferrin receptor expression was significantly upregulated in endometrial cancer tissues compared to adjacent nontumor tissues, and high transferrin receptor levels were associated with poor prognosis. Functional studies revealed that transferrin receptor knockdown impaired endometrial cancer cell proliferation in vitro and in vivo, while transferrin receptor overexpression enhanced endometrial cancer cell proliferation. Mechanistically, transferrin receptor activated the PI3K/AKT/mTOR signaling pathway, as its knockdown suppressed the pathway, and rapamycin, an mTOR inhibitor, reversed transferrin receptor-induced pathway activation and proliferation. Modulation of the labile iron pool by ferric ammonium citrate (FAC) or deferoxamine (DFO) rescued transferrin receptor-induced biological effects. Additionally, AURKA was identified as a regulator of transferrin receptor expression. These findings demonstrate the oncogenic role of transferrin receptor in endometrial cancer and suggest that targeting iron homeostasis and the PI3K/AKT/mTOR pathway may represent potential therapeutic strategies for endometrial cancer.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1352-1365"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532016","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}

引用次数: 0

Insights From Nonsense-Mediated mRNA Decay for Prognosis in Homologous Recombination-Deficient Ovarian Cancer 从无义基因介导的 mRNA 衰变洞察同源重组缺陷卵巢癌的预后

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-01 DOI: 10.1111/cas.70034

Lei Han, Jialing Liu, Runjiao Zhang, Yanan Cheng, Li Dong, Lijuan Wei, Juntian Liu, Ke Wang, Jinpu Yu

{"title":"Insights From Nonsense-Mediated mRNA Decay for Prognosis in Homologous Recombination-Deficient Ovarian Cancer","authors":"Lei Han, Jialing Liu, Runjiao Zhang, Yanan Cheng, Li Dong, Lijuan Wei, Juntian Liu, Ke Wang, Jinpu Yu","doi":"10.1111/cas.70034","DOIUrl":"10.1111/cas.70034","url":null,"abstract":"Not all ovarian cancer patients with homologous recombination deficiency, especially those with germline BRCA mutations, can benefit from platinum-based and targeted therapy. Our study aimed to determine the value of nonsense-mediated mRNA decay, which targeted these mutations. The retrospective analysis of 797 ovarian cancer patients was performed using two public cohorts and one in-house cohort. We developed a prediction algorithm for nonsense-mediated mRNA decay to discriminate between trigger and escape status, finding that escape status indicated a better prognosis. Subsequently, we analyzed differential gene expression and functional pathways between the two statuses and filtered 8 genes associated with the cell cycle. Then the optimized key gene model was built using integrated machine learning algorithms (mean AUC > 0.89), which had a higher independent prognostic value for ovarian cancer with germline BRCA variants or homologous recombination deficiency than the nonsense-mediated mRNA decay algorithm. Furthermore, we classified patients into high- and low-risk groups by the machine learning model and found that the low-risk group had a better prognosis with higher drug response and immune levels of activated dendritic cells than the high-risk controls. Our findings provide a perspective based on nonsense-mediated mRNA decay and cell cycle pathways to distinguish subtypes of germline BRCA or homologous recombination deficiency.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1449-1463"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532084","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}

引用次数: 0

High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells Treg细胞的高抗原性通过在Treg细胞中高PD-1表达赋予PD-1阻断治疗抗性。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-27 DOI: 10.1111/cas.70029

Hiroaki Matsuura, Takamasa Ishino, Toshifumi Ninomiya, Kiichiro Ninomiya, Kota Tachibana, Akiko Honobe-Tabuchi, Yoshinori Muto, Takashi Inozume, Youki Ueda, Kadoaki Ohashi, Yoshinobu Maeda, Joji Nagasaki, Yosuke Togashi

{"title":"High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells","authors":"Hiroaki Matsuura, Takamasa Ishino, Toshifumi Ninomiya, Kiichiro Ninomiya, Kota Tachibana, Akiko Honobe-Tabuchi, Yoshinori Muto, Takashi Inozume, Youki Ueda, Kadoaki Ohashi, Yoshinobu Maeda, Joji Nagasaki, Yosuke Togashi","doi":"10.1111/cas.70029","DOIUrl":"10.1111/cas.70029","url":null,"abstract":"Regulatory T (Treg) cells have an immunosuppressive function, and programmed death-1 (PD-1)-expressing Treg cells reportedly induce resistance to PD-1 blockade therapies through their reactivation. However, the effects of antigenicity on PD-1 expression in Treg cells and the resistance to PD-1 blockade therapy remain unclear. Here, we show that Treg cells gain high PD-1 expression through an antigen with high antigenicity. Additionally, tumors with high antigenicity for Treg cells were resistant to PD-1 blockade in vivo due to PD-1+ Treg-cell infiltration. Because such PD-1+ Treg cells have high cytotoxic T lymphocyte antigen (CTLA)-4 expression, resistance could be overcome by combination with an anti-CTLA-4 monoclonal antibody (mAb). Patients who responded to combination therapy with anti-PD-1 and anti-CTLA-4 mAbs sequentially after primary resistance to PD-1 blockade monotherapy showed high Treg cell infiltration. We propose that the high antigenicity of Treg cells confers resistance to PD-1 blockade therapy via high PD-1 expression in Treg cells, which can be overcome by combination therapy with an anti-CTLA-4 mAb.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1214-1226"},"PeriodicalIF":4.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524896","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}

引用次数: 0

Cytoplasmic Vacuolization: A Fascinating Morphological Alteration From Cellular Stress to Cell Death 细胞质空泡化：从细胞应激到细胞死亡的一个令人着迷的形态学改变。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-27 DOI: 10.1111/cas.70013

Xiaoxu Wen, Hongru Ma

引用次数: 0

EPHB2 Promotes the Progression of Oral Squamous Cell Carcinoma Cells Through the Activation of VPS4A-Mediated Autophagy EPHB2通过激活vps4a介导的自噬促进口腔鳞状细胞癌细胞的进展。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-27 DOI: 10.1111/cas.70033

Yongchun Peng, Jianbo Zhang, Haoxuan Guo, Zhijing He, Yi Jiang, Sheng Zhang, Tengfei Fan

{"title":"EPHB2 Promotes the Progression of Oral Squamous Cell Carcinoma Cells Through the Activation of VPS4A-Mediated Autophagy","authors":"Yongchun Peng, Jianbo Zhang, Haoxuan Guo, Zhijing He, Yi Jiang, Sheng Zhang, Tengfei Fan","doi":"10.1111/cas.70033","DOIUrl":"10.1111/cas.70033","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck neoplasm distinguished by a high risk of metastasis and a poor prognosis. Nevertheless, the fundamental mechanisms of OSCC cell proliferation and metastasis remain poorly understood. Autophagy, as the principal intracellular degradation system, has been implicated in OSCC progression; however, its underlying mechanism remains unclear. In this study, transcriptomic sequencing analysis was performed using both The Cancer Genome Atlas (TCGA) database and samples from OSCC patients and revealed significant upregulation of EPHB2 expression, which is positively correlated with OSCC metastasis and a poor prognosis. In subsequent studies, we observed that the knockdown of EPHB2 resulted in the blockade of autophagic flux due to impaired lysosomal function, leading to inhibited proliferation, migration, and invasion in OSCC cells. Furthermore, the knockdown of EPHB2 significantly suppressed the expression of VPS4A, a key mediator that facilitates autolysosomal degradation. The overexpression of VPS4A restored lysosomal function and autophagic flux, thereby attenuating the inhibitory effects of EPHB2 knockdown on OSCC cell progression. The findings of this study demonstrate that the molecular mechanism underlying EPHB2 regulation of autophagic flux to promote OSCC progression is by regulating VPS4A activity and that EPHB2 may be a diagnostic biomarker and therapeutic target for OSCC prevention and treatment.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1308-1323"},"PeriodicalIF":4.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524895","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}

引用次数: 0

Impact of Tertiary Lymphoid Structure on Prognosis and Tumor Microenvironment in Undifferentiated Pleomorphic Sarcoma 三级淋巴结构对未分化多形性肉瘤预后及肿瘤微环境的影响。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-25 DOI: 10.1111/cas.70018

Hiroki Sonoda, Takeshi Iwasaki, Shin Ishihara, Taro Mori, Yasuharu Nakashima, Yoshinao Oda

{"title":"Impact of Tertiary Lymphoid Structure on Prognosis and Tumor Microenvironment in Undifferentiated Pleomorphic Sarcoma","authors":"Hiroki Sonoda, Takeshi Iwasaki, Shin Ishihara, Taro Mori, Yasuharu Nakashima, Yoshinao Oda","doi":"10.1111/cas.70018","DOIUrl":"10.1111/cas.70018","url":null,"abstract":"Undifferentiated pleomorphic sarcoma (UPS) has a favorable objective response rate to anti-PD-1 drugs compared with other sarcomas. Tertiary lymphoid structure (TLS) is a favorable prognostic factor and a biomarker for immune checkpoint inhibitors (ICIs). Nevertheless, there are limited data on the tumor microenvironment (TME) to support a good response to ICIs in sarcoma. Therefore, this study was conducted to investigate the impact of TLS on prognosis and TME. A total of 52 of UPS with wide resection were divided into intratumoral TLS, extratumoral TLS, and without TLS groups. Survival analysis and immunohistochemistry were performed to evaluate immune cells and immune checkpoint molecules, and multiplexed immunofluorescence was conducted to evaluate T-cell exhaustion among the three groups. TLS was detected in 34 cases (65%), including 23 intratumoral TLS (44%) and 11 extratumoral TLS (21%) cases. Patients with TLS had significantly longer overall survival than those without TLS (log rank p = 0.020). The intratumoral TLS group had a significantly higher number of immune cells and higher expression of PD-L1 and IDO-1 than the without TLS group. Progenitor-exhausted T cells were also observed in patients with UPS. In conclusion, these findings could help predict prognosis in patients with UPS. TLS was demonstrated to be a favorable prognostic factor in patients with UPS. Intratumoral TLS may be a biomarker for the response to ICIs, especially anti-PD-1 drugs.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1464-1473"},"PeriodicalIF":4.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505256","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}

引用次数: 0

Loss of Tapasin in Tumors Potentiates T-Cell Recognition and Anti-Tumor Effects of Immune Checkpoint Blockade 肿瘤中Tapasin的缺失增强了t细胞识别和免疫检查点阻断的抗肿瘤作用。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-24 DOI: 10.1111/cas.70027

Keigo Moniwa, Serina Tokita, Toshiyuki Sumi, Hiroshi Saijo, Shintaro Sugita, Kotomi Arioka, Yoshihiko Hirohashi, Hirofumi Chiba, Takayuki Kanaseki, Toshihiko Torigoe

{"title":"Loss of Tapasin in Tumors Potentiates T-Cell Recognition and Anti-Tumor Effects of Immune Checkpoint Blockade","authors":"Keigo Moniwa, Serina Tokita, Toshiyuki Sumi, Hiroshi Saijo, Shintaro Sugita, Kotomi Arioka, Yoshihiko Hirohashi, Hirofumi Chiba, Takayuki Kanaseki, Toshihiko Torigoe","doi":"10.1111/cas.70027","DOIUrl":"10.1111/cas.70027","url":null,"abstract":"Tumors can evade host immune surveillance by compromising the intracellular antigen processing machinery (APM), such as beta 2 macroglobulin (β2m) or the transporter associated with antigen processing (TAP). Defects in the APM generally result in the downregulation of surface MHC class I (MHC-I) levels. Here, we show that the downregulation of a component of the peptide loading complex (PLC), tapasin, in tumors conversely induces CD8+ T-cell responses and inhibits tumor growth in vivo. Loss of tapasin enhanced the anti-tumor effects of immune checkpoint blockade (ICB) in mouse non-small cell lung and colon cancer models. In contrast to β2m-deficient tumors, the reduced levels of MHC-I in tapasin-deficient tumors were restored by IFN-γ treatment, allowing them to be recognized by CD8+ T cells. These results suggest the presence of a reactive CD8+ T-cell fraction and the ability of immune surveillance to eliminate tumor variants with impaired tapasin expression.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1203-1213"},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484330","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}

引用次数: 0

Novel CHI3L1-Associated Angiogenic Phenotypes Define Glioma Microenvironments: Insights From Multi-Omics Integration 新的chi3l1相关的血管生成表型定义胶质瘤微环境：来自多组学整合的见解。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-24 DOI: 10.1111/cas.70028

Yu-Hang Zhao, Yu-Xiang Cai, Zhi-Yong Pan, Feng Tang, Chao Ma, Ze-Fen Wang, Gang Li, Hang Chang, Su-Fang Tian, Zhi-Qiang Li

{"title":"Novel CHI3L1-Associated Angiogenic Phenotypes Define Glioma Microenvironments: Insights From Multi-Omics Integration","authors":"Yu-Hang Zhao, Yu-Xiang Cai, Zhi-Yong Pan, Feng Tang, Chao Ma, Ze-Fen Wang, Gang Li, Hang Chang, Su-Fang Tian, Zhi-Qiang Li","doi":"10.1111/cas.70028","DOIUrl":"10.1111/cas.70028","url":null,"abstract":"The CHI3L1 signaling pathway significantly influences glioma angiogenesis, but its role in the tumor microenvironment (TME) remains elusive. We propose a novel CHI3L1-associated vascular phenotype classification for glioma through integrative analyses of multiple datasets with bulk and single-cell transcriptome, genomics, digital pathology, and clinical data. We investigated the biological characteristics, genomic alterations, therapeutic vulnerabilities, and immune profiles within these phenotypes through a comprehensive multi-omics approach. We constructed the vascular-related risk (VR) score based on CHI3L1-associated vascular signatures (CAVS) identified by machine learning algorithms. Utilizing unsupervised consensus clustering, gliomas were stratified into three distinct vascular phenotypes: Cluster A, marked by high vascularization and stromal activation with a relatively low levels of tumor-infiltrating lymphocytes (TILs); Cluster B, characterized by moderate vascularization and stromal activity, coupled with a high density of TILs; and Cluster C, defined by low vascularization and sparse immune cell infiltration. We observed that the CAVS effectively indicated glioma-associated angiogenesis and immune suppression by single-cell RNA-seq analysis. Moreover, the high-VR-score group exhibited enhanced angiogenic activity, reduced immune response, resistance to immunotherapy, and poorer clinical outcomes. The VR score independently predicted glioma prognosis and, combined with a nomogram, provided a robust clinical decision-making tool. Potential drug prediction based on transcription factors for high-risk patients was also performed. Our study reveals that CHI3L1-associated vascular phenotypes shape distinct immune landscapes in gliomas, offering insights for optimizing therapeutic strategies to improve patient outcomes.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1433-1448"},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484334","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}

引用次数: 0

NEK2 Control of Esophageal Squamous Cell Carcinoma Growth Based on Circadian Oscillation 基于昼夜振荡的NEK2控制食管鳞状细胞癌的生长。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-18 DOI: 10.1111/cas.16461

Boning Zeng, Chao Sun, Nan Li, Qiuling Chen, Manni Rao, Kai Li, Xiaodi Liu, Shouxia Xie, Jiwu Cheng, Shaoxiang Wang, Xiao Wang

{"title":"NEK2 Control of Esophageal Squamous Cell Carcinoma Growth Based on Circadian Oscillation","authors":"Boning Zeng, Chao Sun, Nan Li, Qiuling Chen, Manni Rao, Kai Li, Xiaodi Liu, Shouxia Xie, Jiwu Cheng, Shaoxiang Wang, Xiao Wang","doi":"10.1111/cas.16461","DOIUrl":"10.1111/cas.16461","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is a globally prevalent malignancy known for its aggressive nature and unfavorable outcomes. Identifying new biomarkers is crucial for the early detection and improved prognostication of ESCC. The circadian clock and NIMA-related kinase 2 (NEK2) are pivotal in cancer development. While the impact of circadian rhythm disruptions on ESCC progression is evident, the specific contribution of NEK2 to these changes is not well understood. Our study discovered NEK2 as a consistently differentially expressed gene across multiple datasets, with elevated expression in ESCC tissues. Notably, NEK2 overexpression was linked to increased ESCC cell proliferation, whereas its inhibition led to reduced cell growth and proliferation. Pathway analyses, including KEGG and Gene Set Enrichment Analysis (GSEA), indicated NEK2's association with established pathways like the cell cycle, and intriguingly, identified the circadian rhythm as a novel pathway influenced by NEK2. RNA sequencing data demonstrated NEK2's circadian rhythmic expression, and subsequent in vitro experiments confirmed its oscillation in synchronized ESCC cells. Moreover, we found a positive correlation between the efficacy of the NEK2 inhibitor INH6 and NEK2 expression levels in ESCC. In conclusion, our findings position NEK2 as a time-dependent oncogene and a potential biomarker in ESCC, highlighting its role in both tumorigenesis and the circadian rhythm.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1282-1294"},"PeriodicalIF":4.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442540","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}

引用次数: 0

CXCL9 and CXCL13 shape endometrial cancer immune-activated microenvironment via tertiary lymphoid structure formation CXCL9和CXCL13通过三级淋巴样结构形成形成子宫内膜癌免疫激活微环境。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-17 DOI: 10.1111/cas.16371

Yoshihiro Nagase, Makoto Kodama, Eriko Aimono, Kohei Nakamura, Reika Takamatsu, Keiko Abe, Takuma Yoshimura, Tatsuyuki Chiyoda, Wataru Yamagami, Hiroshi Nishihara

{"title":"CXCL9 and CXCL13 shape endometrial cancer immune-activated microenvironment via tertiary lymphoid structure formation","authors":"Yoshihiro Nagase, Makoto Kodama, Eriko Aimono, Kohei Nakamura, Reika Takamatsu, Keiko Abe, Takuma Yoshimura, Tatsuyuki Chiyoda, Wataru Yamagami, Hiroshi Nishihara","doi":"10.1111/cas.16371","DOIUrl":"10.1111/cas.16371","url":null,"abstract":"Immune checkpoint inhibitor (ICI) therapy has been successfully applied to various cancers; however, not all patients respond to ICI therapy. Tumors with an immune-activated environment are highly responsive to ICIs. To identify the cells and molecules essential to the formation of an immune-activated cancer microenvironment, we focused on the tertiary lymphoid structure (TLS) and performed histological and genomic analyses using endometrial cancer material. In the high immunogenic group, numerous TLSs were observed, and CXCL9 and CXCL13 expression was markedly increased. CXCL9-positive antigen-presenting and CXCL13-positive follicular dendritic cells were distributed in the T- and B-cell zones of TLSs, respectively. A group of molecules whose expression was upregulated along with CXCL9 and CXCL13 expression was strongly associated with cellular immunity. These results suggest that CXCL9-expressing antigen-presenting cells and CXCL13-expressing follicular dendritic cells coordinately shape the immune-activated microenvironment through TLS formation. The current findings will contribute to a better understanding of the mechanisms underlying the activated cancer immune microenvironment, thereby advancing the field of precision cancer medicine.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1193-1202"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442538","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}

引用次数: 0