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Integrating priorities at the intersection of cancer and neuroscience 整合癌症与神经科学交叉领域的优先事项
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-17 DOI: 10.1016/j.ccell.2024.09.014
William L. Hwang, Ella N. Perrault, Alexander Birbrair, Brandi J. Mattson, David H. Gutmann, Donald J. Mabbott, Edna Cukierman, Elizabeth A. Repasky, Erica K. Sloan, Hui Zong, Ihsan Ekin Demir, Jami L. Saloman, Jeremy C. Borniger, Jian Hu, Jorg Dietrich, Joshua J. Breunig, Kaan Çifcibaşı, Khalil Ali Ahmad Kasm, Manuel Valiente, Max Wintermark, Moran Amit
{"title":"Integrating priorities at the intersection of cancer and neuroscience","authors":"William L. Hwang, Ella N. Perrault, Alexander Birbrair, Brandi J. Mattson, David H. Gutmann, Donald J. Mabbott, Edna Cukierman, Elizabeth A. Repasky, Erica K. Sloan, Hui Zong, Ihsan Ekin Demir, Jami L. Saloman, Jeremy C. Borniger, Jian Hu, Jorg Dietrich, Joshua J. Breunig, Kaan Çifcibaşı, Khalil Ali Ahmad Kasm, Manuel Valiente, Max Wintermark, Moran Amit","doi":"10.1016/j.ccell.2024.09.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.014","url":null,"abstract":"Cancer neuroscience is a rapidly growing multidisciplinary field that conceptualizes tumors as tissues fully integrated into the nervous system. Recognizing the complexity and challenges in this field is of fundamental importance to achieving the goal of translational impact for cancer patients. Our commentary highlights key scientific priorities, optimal training settings, and roadblocks to translating scientific findings to the clinic in this emerging field, aiming to formulate a transformative and cohesive path forward.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"2 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444124","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
A pan-cancer single-cell RNA-seq atlas of intratumoral B cells 肿瘤内 B 细胞的泛癌症单细胞 RNA 序列图谱
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-14 DOI: 10.1016/j.ccell.2024.09.011
Evelyn Fitzsimons, Danwen Qian, Andrei Enica, Krupa Thakkar, Marcellus Augustine, Samuel Gamble, James L. Reading, Kevin Litchfield
{"title":"A pan-cancer single-cell RNA-seq atlas of intratumoral B cells","authors":"Evelyn Fitzsimons, Danwen Qian, Andrei Enica, Krupa Thakkar, Marcellus Augustine, Samuel Gamble, James L. Reading, Kevin Litchfield","doi":"10.1016/j.ccell.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.011","url":null,"abstract":"Tumor-infiltrating B cells play a significant role in tumor development, progression, and prognosis, yet a comprehensive classification system is lacking. To address this gap, we present a pan-cancer single-cell RNA sequencing (scRNA-seq) atlas of tumor-infiltrating B and plasma cells across a large sample cohort. We identify key B cell subset signatures, revealing distinct subpopulations and highlighting the heterogeneity and functional diversity of these cells in the tumor microenvironment. We explore associations between B cell subsets and checkpoint inhibitor therapy responses, finding subset-specific effects on overall response. Additionally, we examine B and T cell crosstalk, identifying unique ligand-receptor pairs for specific B cell subsets, spatially validated. This comprehensive dataset serves as a valuable resource, providing a detailed atlas that enhances the understanding of B cell complexity in tumors and opens new avenues for research and therapeutic strategies.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"229 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431225","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
A prospective study of neoadjuvant pembrolizumab plus chemotherapy for resectable esophageal squamous cell carcinoma: The Keystone-001 trial 针对可切除食管鳞状细胞癌的新辅助 pembrolizumab 加化疗的前瞻性研究：Keystone-001 试验
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-14 DOI: 10.1016/j.ccell.2024.09.008
Xiaobin Shang, Yongjie Xie, Jinpu Yu, Chen Zhang, Gang Zhao, Fei Liang, Liang Liu, Weihong Zhang, Runmei Li, Wenwen Yu, Jie Yue, Chuangui Chen, Xiaofeng Duan, Zhao Ma, Zuoyu Chen, Yanjuan Xiong, Fan Yang, Jianyu Xiao, Rui Zhang, Pengpeng Liu, Hongjing Jiang
{"title":"A prospective study of neoadjuvant pembrolizumab plus chemotherapy for resectable esophageal squamous cell carcinoma: The Keystone-001 trial","authors":"Xiaobin Shang, Yongjie Xie, Jinpu Yu, Chen Zhang, Gang Zhao, Fei Liang, Liang Liu, Weihong Zhang, Runmei Li, Wenwen Yu, Jie Yue, Chuangui Chen, Xiaofeng Duan, Zhao Ma, Zuoyu Chen, Yanjuan Xiong, Fan Yang, Jianyu Xiao, Rui Zhang, Pengpeng Liu, Hongjing Jiang","doi":"10.1016/j.ccell.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.008","url":null,"abstract":"In this phase II study, 47 patients with locally advanced, resectable esophageal squamous cell carcinoma (ESCC) received three cycles of pembrolizumab plus chemotherapy, followed by Da Vinci robot-assisted surgery. The primary endpoints were safety and major pathological response (MPR). Key secondary endpoints included complete pathological response (pCR) and survival. No grade ≥3 adverse events or surgical delays occurred during neoadjuvant therapy. Among 46 patients studied for efficacy, the MPR and pCR rates were 72% and 41%, respectively. After a median follow-up of 27.2 months, the 2-year overall survival (OS) and disease-free survival (DFS) rates were 91% and 89%, respectively. Expansion of TRGC2<sup>+</sup> NKT cells in peripheral blood correlated with neoadjuvant treatment effectiveness, which was validated by <em>in vitro</em> organoid experiments and external cancer datasets, and its functional classification and mechanism of action were further explored. These findings show preoperative pembrolizumab plus chemotherapy is a promising therapeutic strategy for resectable ESCC.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"29 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431224","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
B cell heterogeneity in cancer comes of age 癌症中的 B 细胞异质性时代来临
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-14 DOI: 10.1016/j.ccell.2024.09.013
Colleen Sturdevant, Yuliya Pylayeva-Gupta
{"title":"B cell heterogeneity in cancer comes of age","authors":"Colleen Sturdevant, Yuliya Pylayeva-Gupta","doi":"10.1016/j.ccell.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.013","url":null,"abstract":"The role of B cells in cancer remains incompletely understood. Three recent publications, including a study by Fitzsimons et al. in this issue of <em>Cancer Cell</em>,<span><span><sup>1</sup></span></span> use single-cell RNA sequencing to define pan-cancer atlases of tumor-infiltrating B cell subsets, paving the way for profound advances in our understanding of B cell-dependent antitumor immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"9 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431226","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
The hallmarks of cancer immune evasion 癌症免疫逃避的特征
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-10 DOI: 10.1016/j.ccell.2024.09.010
Claudia Galassi, Timothy A. Chan, Ilio Vitale, Lorenzo Galluzzi
{"title":"The hallmarks of cancer immune evasion","authors":"Claudia Galassi, Timothy A. Chan, Ilio Vitale, Lorenzo Galluzzi","doi":"10.1016/j.ccell.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.010","url":null,"abstract":"According to the widely accepted “three Es” model, the host immune system <u>e</u>liminates malignant cell precursors and contains microscopic neoplasms in a dynamic <u>e</u>quilibrium, preventing cancer outgrowth until neoplastic cells acquire genetic or epigenetic alterations that enable immune <u>e</u>scape. This immunoevasive phenotype originates from various mechanisms that can be classified under a novel “three Cs” conceptual framework: (1) <u>c</u>amouflage, which hides cancer cells from immune recognition, (2) <u>c</u>oercion, which directly or indirectly interferes with immune effector cells, and (3) <u>c</u>ytoprotection, which shields malignant cells from immune cytotoxicity. Blocking the ability of neoplastic cells to evade the host immune system is crucial for increasing the efficacy of modern immunotherapy and conventional therapeutic strategies that ultimately activate anticancer immunosurveillance. Here, we review key hallmarks of cancer immune evasion under the “three Cs” framework and discuss promising strategies targeting such immunoevasive mechanisms.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"62 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398286","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
Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion 由 TP53 介导的雌激素转化确定乳腺癌对 CDK4/6 抑制的长期反应
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-10 DOI: 10.1016/j.ccell.2024.09.009
Rei Kudo, Anton Safonov, Catherine Jones, Enrico Moiso, Jonathan R. Dry, Hong Shao, Sharanya Nag, Edaise M. da Silva, Selma Yeni Yildirim, Qing Li, Elizabeth O'Connell, Payal Patel, Marie Will, Atsushi Fushimi, Marimar Benitez, Martina Bradic, Li Fan, Harikrishna Nakshatri, Dhivya R. Sudhan, Christopher R. Denz, Sarat Chandarlapaty
{"title":"Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion","authors":"Rei Kudo, Anton Safonov, Catherine Jones, Enrico Moiso, Jonathan R. Dry, Hong Shao, Sharanya Nag, Edaise M. da Silva, Selma Yeni Yildirim, Qing Li, Elizabeth O'Connell, Payal Patel, Marie Will, Atsushi Fushimi, Marimar Benitez, Martina Bradic, Li Fan, Harikrishna Nakshatri, Dhivya R. Sudhan, Christopher R. Denz, Sarat Chandarlapaty","doi":"10.1016/j.ccell.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.009","url":null,"abstract":"Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority of patients experience long-term disease control. Using a large, clinically annotated cohort of patients with metastatic hormone receptor-positive (HR+) breast cancer, we identify <em>TP53</em> loss (27.6%) and <em>MDM2</em> amplification (6.4%) to be associated with lack of long-term disease control. Human breast cancer models reveal that p53 loss does not alter CDK4/6 activity or G1 blockade but instead promotes drug-insensitive p130 phosphorylation by CDK2. The persistence of phospho-p130 prevents DREAM complex assembly, enabling cell-cycle re-entry and tumor progression. Inhibitors of CDK2 can overcome p53 loss, leading to geroconversion and manifestation of senescence phenotypes. Complete inhibition of both CDK4/6 and CDK2 kinases appears to be necessary to facilitate long-term response across genomically diverse HR+ breast cancers.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"8 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398281","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
Accelerated approvals: Early-phase success or premature authorization? 加速审批：早期成功还是过早授权？
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-10-10 DOI: 10.1016/j.ccell.2024.09.005
Xiangyun Mao, G. Caleb Alexander, Guanqiao Li
{"title":"Accelerated approvals: Early-phase success or premature authorization?","authors":"Xiangyun Mao, G. Caleb Alexander, Guanqiao Li","doi":"10.1016/j.ccell.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.005","url":null,"abstract":"We compare the clinical trial success rates of products receiving US Food and Drug Administration (FDA) accelerated approval (AA) to those approved without using this pathway. Our findings raise important questions about how the AA pathway can best optimize early access to therapeutics that are ultimately proven safe and effective.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"227 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398282","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
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":"62 25 1","pages":""},"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":"76 1","pages":""},"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":"5 1","pages":""},"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
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