Nature cancer最新文献

{"title":"Clinical implementation of artificial-intelligence-assisted detection of breast cancer metastases in sentinel lymph nodes: the CONFIDENT-B single-center, non-randomized clinical trial","authors":"C. van Dooijeweert, R. N. Flach, N. D. ter Hoeve, C. P. H. Vreuls, R. Goldschmeding, J. E. Freund, P. Pham, T. Q. Nguyen, E. van der Wall, G. W. J. Frederix, N. Stathonikos, P. J. van Diest","doi":"10.1038/s43018-024-00788-z","DOIUrl":"10.1038/s43018-024-00788-z","url":null,"abstract":"Pathologists’ assessment of sentinel lymph nodes (SNs) for breast cancer (BC) metastases is a treatment-guiding yet labor-intensive and costly task because of the performance of immunohistochemistry (IHC) in morphologically negative cases. This non-randomized, single-center clinical trial (International Standard Randomized Controlled Trial Number:14323711) assessed the efficacy of an artificial intelligence (AI)-assisted workflow for detecting BC metastases in SNs while maintaining diagnostic safety standards. From September 2022 to May 2023, 190 SN specimens were consecutively enrolled and allocated biweekly to the intervention arm (n = 100) or control arm (n = 90). In both arms, digital whole-slide images of hematoxylin–eosin sections of SN specimens were assessed by an expert pathologist, who was assisted by the ‘Metastasis Detection’ app (Visiopharm) in the intervention arm. Our primary endpoint showed a significantly reduced adjusted relative risk of IHC use (0.680, 95% confidence interval: 0.347–0.878) for AI-assisted pathologists, with subsequent cost savings of ~3,000 €. Secondary endpoints showed significant time reductions and up to 30% improved sensitivity for AI-assisted pathologists. This trial demonstrates the safety and potential for cost and time savings of AI assistance. Van Dooijeweert et al. conducted a prospective study on the clinical implementation of artificial-intelligence-assisted detection of sentinel lymph node metastasis in persons with breast cancer and report on its effects, including on time and cost.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 8","pages":"1195-1205"},"PeriodicalIF":23.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43018-024-00788-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological targeting of the cancer epigenome","authors":"Nathaniel W. Mabe, Jennifer A. Perry, Clare F. Malone, Kimberly Stegmaier","doi":"10.1038/s43018-024-00777-2","DOIUrl":"10.1038/s43018-024-00777-2","url":null,"abstract":"Epigenetic dysregulation is increasingly appreciated as a hallmark of cancer, including disease initiation, maintenance and therapy resistance. As a result, there have been advances in the development and evaluation of epigenetic therapies for cancer, revealing substantial promise but also challenges. Three epigenetic inhibitor classes are approved in the USA, and many more are currently undergoing clinical investigation. In this Review, we discuss recent developments for each epigenetic drug class and their implications for therapy, as well as highlight new insights into the role of epigenetics in cancer. Stegmaier and colleagues provide a review on the latest development in targeting the cancer epigenome, give an overview of distinct drug classes, and discuss therapeutic possibilities and challenges.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 6","pages":"844-865"},"PeriodicalIF":23.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469520","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}

{"title":"Targeting HIF-1 to treat AML","authors":"Darragh Flood, Cormac T. Taylor","doi":"10.1038/s43018-024-00779-0","DOIUrl":"10.1038/s43018-024-00779-0","url":null,"abstract":"Acute myeloid leukemia (AML) is an aggressive hematological cancer with limited treatment options. A study now provides compelling data and develops a therapeutic approach of targeting AML with a prolyl hydroxylase inhibitor, a strategy based on the sensitivity of myeloid cells to modulation of the transcription factor HIF.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 6","pages":"821-822"},"PeriodicalIF":23.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469521","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}

{"title":"Milestones in tumor vascularization and its therapeutic targeting","authors":"Michele De Palma, Douglas Hanahan","doi":"10.1038/s43018-024-00780-7","DOIUrl":"10.1038/s43018-024-00780-7","url":null,"abstract":"Research into the mechanisms and manifestations of solid tumor vascularization was launched more than 50 years ago with the proposition and experimental demonstrations that angiogenesis is instrumental for tumor growth and was, therefore, a promising therapeutic target. The biological knowledge and therapeutic insights forthcoming have been remarkable, punctuated by new concepts, many of which were not foreseen in the early decades. This article presents a perspective on tumor vascularization and its therapeutic targeting but does not portray a historical timeline. Rather, we highlight eight conceptual milestones, integrating initial discoveries and recent progress and posing open questions for the future. De Palma and Hanahan outline advances in understanding tumor angiogenesis and discuss the therapeutic opportunities of targeting tumor vascularization.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 6","pages":"827-843"},"PeriodicalIF":23.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450855","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}

{"title":"Multidimensional analysis reveals predictive markers for CAR-T efficacy","authors":"Kevin P. Letscher, Sai T. Reddy","doi":"10.1038/s43018-024-00785-2","DOIUrl":"10.1038/s43018-024-00785-2","url":null,"abstract":"At present, six CAR-T therapies are FDA approved to treat hematological cancers, but not all patients respond. A new study has developed a multidimensional functional profiling method to screen CAR-T cells from patients with large B cell lymphomas in clinical trials and identified a T cell subset associated with successful clinical response.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 7","pages":"960-961"},"PeriodicalIF":23.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432277","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}

{"title":"Author Correction: Direct and selective pharmacological disruption of the YAP–TEAD interface by IAG933 inhibits Hippo-dependent and RAS–MAPK-altered cancers","authors":"Emilie A. Chapeau, Laurent Sansregret, Giorgio G. Galli, Patrick Chène, Markus Wartmann, Thanos P. Mourikis, Patricia Jaaks, Sabrina Baltschukat, Ines A. M. Barbosa, Daniel Bauer, Saskia M. Brachmann, Clara Delaunay, Claire Estadieu, Jason E. Faris, Pascal Furet, Stefanie Harlfinger, Andreas Hueber, Eloísa Jiménez Núñez, David P. Kodack, Emeline Mandon, Typhaine Martin, Yannick Mesrouze, Vincent Romanet, Clemens Scheufler, Holger Sellner, Christelle Stamm, Dario Sterker, Luca Tordella, Francesco Hofmann, Nicolas Soldermann, Tobias Schmelzle","doi":"10.1038/s43018-024-00797-y","DOIUrl":"10.1038/s43018-024-00797-y","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 7","pages":"1130-1130"},"PeriodicalIF":23.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleotide metabolism in cancer cells fuels a UDP-driven macrophage cross-talk, promoting immunosuppression and immunotherapy resistance","authors":"Tommaso Scolaro, Marta Manco, Mathieu Pecqueux, Ricardo Amorim, Rosa Trotta, Heleen H. Van Acker, Matthias Van Haele, Niranjan Shirgaonkar, Stefan Naulaerts, Jan Daniluk, Fran Prenen, Chiara Varamo, Donatella Ponti, Ginevra Doglioni, Ana Margarida Ferreira Campos, Juan Fernandez Garcia, Silvia Radenkovic, Pegah Rouhi, Aleksandar Beatovic, Liwei Wang, Yu Wang, Amalia Tzoumpa, Asier Antoranz, Ara Sargsian, Mario Di Matteo, Emanuele Berardi, Jermaine Goveia, Bart Ghesquière, Tania Roskams, Stefaan Soenen, Thomas Voets, Bella Manshian, Sarah-Maria Fendt, Peter Carmeliet, Abhishek D. Garg, Ramanuj DasGupta, Baki Topal, Massimiliano Mazzone","doi":"10.1038/s43018-024-00771-8","DOIUrl":"10.1038/s43018-024-00771-8","url":null,"abstract":"Many individuals with cancer are resistant to immunotherapies. Here, we identify the gene encoding the pyrimidine salvage pathway enzyme cytidine deaminase (CDA) among the top upregulated metabolic genes in several immunotherapy-resistant tumors. We show that CDA in cancer cells contributes to the uridine diphosphate (UDP) pool. Extracellular UDP hijacks immunosuppressive tumor-associated macrophages (TAMs) through its receptor P2Y6. Pharmacologic or genetic inhibition of CDA in cancer cells (or P2Y6 in TAMs) disrupts TAM-mediated immunosuppression, promoting cytotoxic T cell entry and susceptibility to anti-programmed cell death protein 1 (anti-PD-1) treatment in resistant pancreatic ductal adenocarcinoma (PDAC) and melanoma models. Conversely, CDA overexpression in CDA-depleted PDACs or anti-PD-1-responsive colorectal tumors or systemic UDP administration (re)establishes resistance. In individuals with PDAC, high CDA levels in cancer cells correlate with increased TAMs, lower cytotoxic T cells and possibly anti-PD-1 resistance. In a pan-cancer single-cell atlas, CDAhigh cancer cells match with T cell cytotoxicity dysfunction and P2RY6high TAMs. Overall, we suggest CDA and P2Y6 as potential targets for cancer immunotherapy. Scolaro et al. identify the enzyme cytidine deaminase (CDA) as upregulated in immunotherapy-resistant tumors and find it contributes to the UDP pool, which in turn modulates tumor-associated macrophages to instruct an immune-evasive TME.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 8","pages":"1206-1226"},"PeriodicalIF":23.5,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43018-024-00771-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-associated macrophages restrict CD8+ T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment","authors":"Kevin M. Tharp, Kelly Kersten, Ori Maller, Greg A. Timblin, Connor Stashko, Fernando P. Canale, Rosa E. Menjivar, Mary-Kate Hayward, Ilona Berestjuk, Johanna ten Hoeve, Bushra Samad, Alastrair J. Ironside, Marina Pasca di Magliano, Alexander Muir, Roger Geiger, Alexis J. Combes, Valerie M. Weaver","doi":"10.1038/s43018-024-00775-4","DOIUrl":"10.1038/s43018-024-00775-4","url":null,"abstract":"Tumor progression is accompanied by fibrosis, a condition of excessive extracellular matrix accumulation, which is associated with diminished antitumor immune infiltration. Here we demonstrate that tumor-associated macrophages (TAMs) respond to the stiffened fibrotic tumor microenvironment (TME) by initiating a collagen biosynthesis program directed by transforming growth factor-β. A collateral effect of this programming is an untenable metabolic milieu for productive CD8+ T cell antitumor responses, as collagen-synthesizing macrophages consume environmental arginine, synthesize proline and secrete ornithine that compromises CD8+ T cell function in female breast cancer. Thus, a stiff and fibrotic TME may impede antitumor immunity not only by direct physical exclusion of CD8+ T cells but also through secondary effects of a mechano-metabolic programming of TAMs, which creates an inhospitable metabolic milieu for CD8+ T cells to respond to anticancer immunotherapies. Weaver and colleagues show that TGFβ-induced collagen deposition and metabolic reprogramming of the breast cancer microenvironment by tumor-associated macrophages restrict the antitumor activity of CD8+ T cells in female breast cancer.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 7","pages":"1045-1062"},"PeriodicalIF":23.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238107","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}

{"title":"Fibrotic tumors tune metabolism for immune evasion","authors":"Matthew D. Perricone, Costas A. Lyssiotis","doi":"10.1038/s43018-024-00758-5","DOIUrl":"10.1038/s43018-024-00758-5","url":null,"abstract":"Tumor fibrosis is known to suppress anti-tumor immunity. A new study now highlights the role of tumor-associated macrophages in coordinating fibrosis-mediated metabolic changes in tumors, restricting cytotoxic T cell responses and contributing to tumor growth.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 7","pages":"955-957"},"PeriodicalIF":23.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238100","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}

{"title":"LORIS robustly predicts patient outcomes with immune checkpoint blockade therapy using common clinical, pathologic and genomic features","authors":"Tian-Gen Chang, Yingying Cao, Hannah J. Sfreddo, Saugato Rahman Dhruba, Se-Hoon Lee, Cristina Valero, Seong-Keun Yoo, Diego Chowell, Luc G. T. Morris, Eytan Ruppin","doi":"10.1038/s43018-024-00772-7","DOIUrl":"10.1038/s43018-024-00772-7","url":null,"abstract":"Despite the revolutionary impact of immune checkpoint blockade (ICB) in cancer treatment, accurately predicting patient responses remains challenging. Here, we analyzed a large dataset of 2,881 ICB-treated and 841 non-ICB-treated patients across 18 solid tumor types, encompassing a wide range of clinical, pathologic and genomic features. We developed a clinical score called LORIS (logistic regression-based immunotherapy-response score) using a six-feature logistic regression model. LORIS outperforms previous signatures in predicting ICB response and identifying responsive patients even with low tumor mutational burden or programmed cell death 1 ligand 1 expression. LORIS consistently predicts patient objective response and short-term and long-term survival across most cancer types. Moreover, LORIS showcases a near-monotonic relationship with ICB response probability and patient survival, enabling precise patient stratification. As an accurate, interpretable method using a few readily measurable features, LORIS may help improve clinical decision-making in precision medicine to maximize patient benefit. LORIS is available as an online tool at https://loris.ccr.cancer.gov/ . Chang et al. performed a pan-cancer multimodal data integration analysis and devised a model, LORIS, that can predict objective responses to immunotherapy and patient survival across many cancer types and allow for patient stratification.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 8","pages":"1158-1175"},"PeriodicalIF":23.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238104","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}