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The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions 高级别浆液性卵巢癌中三级淋巴结构的活性受部位、基质和细胞相互作用的影响
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-10 DOI: 10.1016/j.ccell.2024.09.007
Ian P. MacFawn, Grant Magnon, Grace Gorecki, Sheryl Kunning, Rufiaat Rashid, Medard Ernest Kaiza, Huda Atiya, Ayana T. Ruffin, Sarah Taylor, T. Rinda Soong, Riyue Bao, Lan G. Coffman, Tullia C. Bruno
{"title":"The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions","authors":"Ian P. MacFawn, Grant Magnon, Grace Gorecki, Sheryl Kunning, Rufiaat Rashid, Medard Ernest Kaiza, Huda Atiya, Ayana T. Ruffin, Sarah Taylor, T. Rinda Soong, Riyue Bao, Lan G. Coffman, Tullia C. Bruno","doi":"10.1016/j.ccell.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.007","url":null,"abstract":"Most high grade serous ovarian cancers (HGSOC) originate in the fallopian tube but spread to the ovary and peritoneal cavity, highlighting the need to understand antitumor immunity across HGSOC sites. Using spatial analyses, we discover that tertiary lymphoid structures (TLSs) within ovarian tumors are less developed compared with TLSs in fallopian tube or omental tumors. We reveal transcriptional differences across a spectrum of lymphoid structures, demonstrating that immune cell activity increases when residing in more developed TLSs and produce a prognostic, spatially derived TLS signature from HGSOC tumors. We interrogate TLS-adjacent stroma and assess how normal mesenchymal stem cells MSCs (nMSCs) may support B cell function and TLS, contrary to cancer-educated MSCs (CA-MSCs) which negate the prognostic benefit of our TLS signature, suggesting that pro-tumorigenic stroma could limit TLS formation.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398284","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
Lactylation in cancer: Current understanding and challenges 癌症中的乳化作用：当前的认识和挑战
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-10 DOI: 10.1016/j.ccell.2024.09.006
Hongde Li, Linchong Sun, Ping Gao, Hai Hu
{"title":"Lactylation in cancer: Current understanding and challenges","authors":"Hongde Li, Linchong Sun, Ping Gao, Hai Hu","doi":"10.1016/j.ccell.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.006","url":null,"abstract":"Lactylation, a recently identified post-translational modification, has initially been linked to gene transcription regulation through epigenetic mechanisms. However, its role in tumorigenesis—whether as a major driver or a minor regulator—remains uncertain. Here, we summarize the current understanding of lactylation and discuss the inherent challenges in definitively attributing specific biological roles to this modification. We emphasize the necessity for precise methodologies to manipulate lactylation levels within pathophysiologically relevant conditions. Further investigation is required to determine whether lactylation plays a critical role in tumor biology or merely reflects secondary metabolic alterations.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398285","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
Spark in the darkness: Discovering action potentials in brain tumors 黑暗中的火花发现脑肿瘤中的动作电位
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-03 DOI: 10.1016/j.ccell.2024.09.004
Nikolas Andreas Stevens, Nina Drewa, Varun Venkataramani
{"title":"Spark in the darkness: Discovering action potentials in brain tumors","authors":"Nikolas Andreas Stevens, Nina Drewa, Varun Venkataramani","doi":"10.1016/j.ccell.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.004","url":null,"abstract":"Gliomas exhibit significant molecular diversity and poor prognosis. In this issue of <em>Cancer Cell</em>, Curry et al. apply Patch-seq on human glioma samples uncovering hybrid cells with glial and neuronal features, capable of firing action potentials in isocitrate dehydrogenase mutant gliomas. These findings highlight the importance of neural features in tumor biology and progression.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369150","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
Midkine as a driver of age-related changes and increase in mammary tumorigenesis Midkine 是乳腺肿瘤发生中与年龄有关的变化和增加的驱动因素
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-03 DOI: 10.1016/j.ccell.2024.09.002
Pengze Yan, Ernesto Rojas Jimenez, Zheqi Li, Triet Bui, Marco Seehawer, Jun Nishida, Pierre Foidart, Laura E. Stevens, Yingtian Xie, Miguel Munoz Gomez, So Yeon Park, Henry W. Long, Kornelia Polyak
{"title":"Midkine as a driver of age-related changes and increase in mammary tumorigenesis","authors":"Pengze Yan, Ernesto Rojas Jimenez, Zheqi Li, Triet Bui, Marco Seehawer, Jun Nishida, Pierre Foidart, Laura E. Stevens, Yingtian Xie, Miguel Munoz Gomez, So Yeon Park, Henry W. Long, Kornelia Polyak","doi":"10.1016/j.ccell.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.002","url":null,"abstract":"Aging is a pivotal risk factor for cancer, yet the underlying mechanisms remain poorly defined. Here, we explore age-related changes in the rat mammary gland by single-cell multiomics. Our findings include increased epithelial proliferation, loss of luminal identity, and decreased naive B and T cells with age. We discover a luminal progenitor population unique to old rats with profiles reflecting precancerous changes and identify midkine (<em>Mdk</em>) as a gene upregulated with age and a regulator of age-related luminal progenitors. Midkine treatment of young rats mimics age-related changes via activating PI3K-AKT-SREBF1 pathway and promotes nitroso-N-methylurea-induced mammary tumorigenesis. Midkine levels increase with age in human blood and mammary epithelium, and higher <em>MDK</em> in normal breast tissue is associated with higher breast cancer risk in younger women. Our findings reveal a link between aging and susceptibility to tumor initiation and identify midkine as a mediator of age-dependent increase in breast tumorigenesis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369149","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
Spatial oncology: Translating contextual biology to the clinic 空间肿瘤学：将环境生物学应用于临床
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-03 DOI: 10.1016/j.ccell.2024.09.001
Dennis Gong, Jeanna M. Arbesfeld-Qiu, Ella Perrault, Jung Woo Bae, William L. Hwang
{"title":"Spatial oncology: Translating contextual biology to the clinic","authors":"Dennis Gong, Jeanna M. Arbesfeld-Qiu, Ella Perrault, Jung Woo Bae, William L. Hwang","doi":"10.1016/j.ccell.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.001","url":null,"abstract":"Microscopic examination of cells in their tissue context has been the driving force behind diagnostic histopathology over the past two centuries. Recently, the rise of advanced molecular biomarkers identified through single cell profiling has increased our understanding of cellular heterogeneity in cancer but have yet to significantly impact clinical care. Spatial technologies integrating molecular profiling with microenvironmental features are poised to bridge this translational gap by providing critical <em>in situ</em> context for understanding cellular interactions and organization. Here, we review how spatial tools have been used to study tumor ecosystems and their clinical applications. We detail findings in cell-cell interactions, microenvironment composition, and tissue remodeling for immune evasion and therapeutic resistance. Additionally, we highlight the emerging role of multi-omic spatial profiling for characterizing clinically relevant features including perineural invasion, tertiary lymphoid structures, and the tumor-stroma interface. Finally, we explore strategies for clinical integration and their augmentation of therapeutic and diagnostic approaches.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369676","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
Midkine links aging with breast cancer—A new predictor of cancer risk Midkine 将衰老与乳腺癌联系起来--癌症风险的新预测指标
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-03 DOI: 10.1016/j.ccell.2024.09.003
Jane E. Visvader
{"title":"Midkine links aging with breast cancer—A new predictor of cancer risk","authors":"Jane E. Visvader","doi":"10.1016/j.ccell.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.003","url":null,"abstract":"Despite aging being one of the strongest risk factors for cancer, little is known about the biological mechanisms that promote tumor initiation. In this issue of <em>Cancer Cell</em>, Yan et al. address this fundamental question in the context of breast cancer and report that midkine is upregulated during the aging process and can promote tumorigenesis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369151","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
Architecture sets the path: Breast cancer subtypes differently shape the early brain metastatic niche 结构决定道路：乳腺癌亚型以不同方式塑造早期脑转移生态位
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-09-26 DOI: 10.1016/j.ccell.2024.08.021
Menno Boon, Leila Akkari
{"title":"Architecture sets the path: Breast cancer subtypes differently shape the early brain metastatic niche","authors":"Menno Boon, Leila Akkari","doi":"10.1016/j.ccell.2024.08.021","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.08.021","url":null,"abstract":"The ability of disseminated cancer cells to colonize the brain is highly dependent on initial survival cues, often evoking early microenvironmental adaptations. In this issue of <em>Cancer Cell</em>, Gan et al. unveil disparate tumor architectures in early stage HER2+ breast cancer and triple-negative breast cancer brain metastases that shape stromal interactions, providing a rationale for subtype-dependent patient stratification.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321130","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
Universal and tissue-specific fibroblasts in chronic inflammation and cancer 慢性炎症和癌症中的通用和组织特异性成纤维细胞
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-09-26 DOI: 10.1016/j.ccell.2024.08.022
Simon Koplev, Sarah A. Teichmann
{"title":"Universal and tissue-specific fibroblasts in chronic inflammation and cancer","authors":"Simon Koplev, Sarah A. Teichmann","doi":"10.1016/j.ccell.2024.08.022","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.08.022","url":null,"abstract":"In this issue of <em>Cancer Cell</em>, Gao et al. map fibroblast diversity across tumors and chronic inflammatory tissues. The authors uncover universal fibroblast subtypes such as LRRC15<sup>+</sup> and MMP1<sup>+</sup> myofibroblasts along with specialized tissue-specific subtypes. They reveal cellular roles of fibroblasts in immunosuppression through stromal niches and cell-cell interactions.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321128","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
Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer 凝血因子 X 可增强前列腺癌患者对雄激素剥夺疗法的抵抗力
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-09-19 DOI: 10.1016/j.ccell.2024.08.018
Bianca Calì, Martina Troiani, Silvia Bressan, Giuseppe Attanasio, Sara Merler, Viola Moscarda, Simone Mosole, Elena Ricci, Christina Guo, Wei Yuan, Lewis Gallagher, Arian Lundberg, Ilona Bernett, Ines Figueiredo, Rydell Alvarez Arzola, Ernesto Bermudez Abreut, Mariantonietta D’Ambrosio, Nicolò Bancaro, Daniela Brina, Sara Zumerle, Andrea Alimonti
{"title":"Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer","authors":"Bianca Calì, Martina Troiani, Silvia Bressan, Giuseppe Attanasio, Sara Merler, Viola Moscarda, Simone Mosole, Elena Ricci, Christina Guo, Wei Yuan, Lewis Gallagher, Arian Lundberg, Ilona Bernett, Ines Figueiredo, Rydell Alvarez Arzola, Ernesto Bermudez Abreut, Mariantonietta D’Ambrosio, Nicolò Bancaro, Daniela Brina, Sara Zumerle, Andrea Alimonti","doi":"10.1016/j.ccell.2024.08.018","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.08.018","url":null,"abstract":"<p>Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, <em>F10</em><sup><em>high</em></sup> PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances <em>F10</em> expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246012","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
Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer 核葡萄球菌有助于微卫星稳定型结直肠癌的抗 PD-1 治疗
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-09-19 DOI: 10.1016/j.ccell.2024.08.019
Xueliang Wang, Yi Fang, Wei Liang, Chi Chun Wong, Huanlong Qin, Yaohui Gao, Meinong Liang, Lei Song, Yongxin Zhang, Miao Fan, Chuanfa Liu, Harry Cheuk-Hay Lau, Lixia Xu, Xiaoxing Li, Wu Song, Junlin Wang, Na Wang, Tao Yang, Mengmiao Mo, Xiang Zhang, Jun Yu
{"title":"Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer","authors":"Xueliang Wang, Yi Fang, Wei Liang, Chi Chun Wong, Huanlong Qin, Yaohui Gao, Meinong Liang, Lei Song, Yongxin Zhang, Miao Fan, Chuanfa Liu, Harry Cheuk-Hay Lau, Lixia Xu, Xiaoxing Li, Wu Song, Junlin Wang, Na Wang, Tao Yang, Mengmiao Mo, Xiang Zhang, Jun Yu","doi":"10.1016/j.ccell.2024.08.019","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.08.019","url":null,"abstract":"<p>Microsatellite stable (MSS) colorectal cancers (CRCs) are often resistant to anti-programmed death-1 (PD-1) therapy. Here, we show that a CRC pathogen, <em>Fusobacterium nucleatum</em> (<em>Fn</em>), paradoxically sensitizes MSS CRC to anti-PD-1. Fecal microbiota transplantation (FMT) from patients with <em>Fn</em>-high MSS CRC to germ-free mice bearing MSS CRC confers sensitivity to anti-PD-1 compared to FMT from <em>Fn</em>-low counterparts. Single <em>Fn</em> administration also potentiates anti-PD-1 efficacy in murine allografts and CD34<sup>+</sup>-humanized mice bearing MSS CRC. Mechanistically, we demonstrate that intratumoral <em>Fn</em> generates abundant butyric acid, which inhibits histone deacetylase (HDAC) 3/8 in CD8<sup>+</sup> T cells, inducing <em>Tbx21</em> promoter H3K27 acetylation and expression. TBX21 transcriptionally represses PD-1, alleviating CD8<sup>+</sup> T cell exhaustion and promoting effector function. Supporting this notion, knockout of a butyric acid-producing gene in <em>Fn</em> abolishes its anti-PD-1 boosting effect. In patients with MSS CRC, high intratumoral <em>Fn</em> predicts favorable response to anti-PD-1 therapy, indicating <em>Fn</em> as a potential biomarker of immunotherapy response in MSS CRC.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246245","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
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