Pub Date : 2025-01-09DOI: 10.1038/s43018-024-00846-6
John Nguyen, Francisco Sanchez-Vega
Patients with lung-metastatic pancreatic ductal adenocarcinoma survive longer than those with liver metastases. A study now leverages real-world data to identify distinct molecular and immune profiles that can explain differences in tumor aggressiveness and clinical outcomes.
{"title":"Metastatic patterns stratify patients with pancreatic cancer","authors":"John Nguyen, Francisco Sanchez-Vega","doi":"10.1038/s43018-024-00846-6","DOIUrl":"10.1038/s43018-024-00846-6","url":null,"abstract":"Patients with lung-metastatic pancreatic ductal adenocarcinoma survive longer than those with liver metastases. A study now leverages real-world data to identify distinct molecular and immune profiles that can explain differences in tumor aggressiveness and clinical outcomes.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 1","pages":"16-17"},"PeriodicalIF":23.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952010","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}
Pub Date : 2025-01-09DOI: 10.1038/s43018-024-00896-w
Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin McCurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M. Krajewski, Florian A. Büttner, Matthias Schwab, Daniel Heng, Rafael C. Casellas, Kunal Rai, Niki M. Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K. Choueiri, David A. Braun, Sachet A. Shukla
Immune checkpoint inhibitors can lead to ‘exceptional’, durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF). In the IO/IO cohort, clonal neoantigen load was significantly higher in persons with ER. In the IO/VEGF cohort, ER participants displayed strong enrichment of B cell receptor signaling-related pathways, tertiary lymphoid structure (TLS) signatures and evidence of increased metabolic activity. Our results suggest that ER may be related to clonal neoantigen-driven cytotoxic T cell responses and TLS formation in tumor microenvironments. Therapeutic combinations that elicit both T cell-directed and B cell-directed antitumor immunity may be important to achieve exceptional benefit to IO-based treatment in ccRCC. Shukla and colleagues study the genomic and transcriptomic data of exceptional responders to immunotherapy in renal cell carcinoma and find that such responses could be related to tertiary lymphoid structures, clonal neoantigen load and altered metabolism.
{"title":"Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma","authors":"Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin McCurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M. Krajewski, Florian A. Büttner, Matthias Schwab, Daniel Heng, Rafael C. Casellas, Kunal Rai, Niki M. Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K. Choueiri, David A. Braun, Sachet A. Shukla","doi":"10.1038/s43018-024-00896-w","DOIUrl":"10.1038/s43018-024-00896-w","url":null,"abstract":"Immune checkpoint inhibitors can lead to ‘exceptional’, durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF). In the IO/IO cohort, clonal neoantigen load was significantly higher in persons with ER. In the IO/VEGF cohort, ER participants displayed strong enrichment of B cell receptor signaling-related pathways, tertiary lymphoid structure (TLS) signatures and evidence of increased metabolic activity. Our results suggest that ER may be related to clonal neoantigen-driven cytotoxic T cell responses and TLS formation in tumor microenvironments. Therapeutic combinations that elicit both T cell-directed and B cell-directed antitumor immunity may be important to achieve exceptional benefit to IO-based treatment in ccRCC. Shukla and colleagues study the genomic and transcriptomic data of exceptional responders to immunotherapy in renal cell carcinoma and find that such responses could be related to tertiary lymphoid structures, clonal neoantigen load and altered metabolism.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 2","pages":"372-384"},"PeriodicalIF":23.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952008","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}
Pub Date : 2025-01-09DOI: 10.1038/s43018-024-00881-3
Jason M. Link, Jennifer R. Eng, Carl Pelz, Kevin MacPherson-Hawthorne, Patrick J. Worth, Shamaline Sivagnanam, Dove J. Keith, Sydney Owen, Ellen M. Langer, Alison Grossblatt-Wait, Gustavo Salgado-Garza, Allison L. Creason, Sara Protzek, Julian Egger, Hannah Holly, Michael B. Heskett, Koei Chin, Nell Kirchberger, Konjit Betre, Elmar Bucher, David Kilburn, Zhi Hu, Michael W. Munks, Isabel A. English, Motoyuki Tsuda, Jeremy Goecks, Emek Demir, Andrew C. Adey, Adel Kardosh, Charles D. Lopez, Brett C. Sheppard, Alex Guimaraes, Brian Brinkerhoff, Terry K. Morgan, Gordon B. Mills, Lisa M. Coussens, Jonathan R. Brody, Rosalie C. Sears
Patients with metastatic pancreatic ductal adenocarcinoma survive longer if disease spreads to the lung but not the liver. Here we generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype. We developed a primary organotropism (pORG) gene set enriched in liver cohort versus lung cohort primary tumors. We identified ongoing replication stress response pathways in high pORG/liver cohort tumors, whereas low pORG/lung cohort tumors had greater densities of lymphocytes and shared T cell clonal responses. Our study demonstrates that liver-avid pancreatic ductal adenocarcinoma is associated with tolerance to ongoing replication stress, limited tumor immunity and less-favorable outcomes, whereas low replication stress, lung-avid/liver-averse tumors are associated with active tumor immunity that may account for favorable outcomes. Sears and colleagues found that ongoing replication stress pathways and T cell clonal responses differentiate liver and lung recurrence and are associated with different clinical outcomes in the context of pancreatic ductal adenocarcinoma.
{"title":"Ongoing replication stress tolerance and clonal T cell responses distinguish liver and lung recurrence and outcomes in pancreatic cancer","authors":"Jason M. Link, Jennifer R. Eng, Carl Pelz, Kevin MacPherson-Hawthorne, Patrick J. Worth, Shamaline Sivagnanam, Dove J. Keith, Sydney Owen, Ellen M. Langer, Alison Grossblatt-Wait, Gustavo Salgado-Garza, Allison L. Creason, Sara Protzek, Julian Egger, Hannah Holly, Michael B. Heskett, Koei Chin, Nell Kirchberger, Konjit Betre, Elmar Bucher, David Kilburn, Zhi Hu, Michael W. Munks, Isabel A. English, Motoyuki Tsuda, Jeremy Goecks, Emek Demir, Andrew C. Adey, Adel Kardosh, Charles D. Lopez, Brett C. Sheppard, Alex Guimaraes, Brian Brinkerhoff, Terry K. Morgan, Gordon B. Mills, Lisa M. Coussens, Jonathan R. Brody, Rosalie C. Sears","doi":"10.1038/s43018-024-00881-3","DOIUrl":"10.1038/s43018-024-00881-3","url":null,"abstract":"Patients with metastatic pancreatic ductal adenocarcinoma survive longer if disease spreads to the lung but not the liver. Here we generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype. We developed a primary organotropism (pORG) gene set enriched in liver cohort versus lung cohort primary tumors. We identified ongoing replication stress response pathways in high pORG/liver cohort tumors, whereas low pORG/lung cohort tumors had greater densities of lymphocytes and shared T cell clonal responses. Our study demonstrates that liver-avid pancreatic ductal adenocarcinoma is associated with tolerance to ongoing replication stress, limited tumor immunity and less-favorable outcomes, whereas low replication stress, lung-avid/liver-averse tumors are associated with active tumor immunity that may account for favorable outcomes. Sears and colleagues found that ongoing replication stress pathways and T cell clonal responses differentiate liver and lung recurrence and are associated with different clinical outcomes in the context of pancreatic ductal adenocarcinoma.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 1","pages":"123-144"},"PeriodicalIF":23.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952012","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}
Pub Date : 2025-01-07DOI: 10.1038/s43018-024-00877-z
Loss of CDKN2A is known to drive the progression of several cancers, including esophageal adenocarcinoma (EAC). Genetic analyses of samples of Barrett’s esophagus (EAC precursor condition) show that early loss of CDKN2A delays EAC initiation. Moreover, the concomitant loss of other genes in the same chromosomal locus has different effects depending on context.
{"title":"Effects of CDKN2A loss on evolution of esophageal adenocarcinoma depend on context and time","authors":"","doi":"10.1038/s43018-024-00877-z","DOIUrl":"10.1038/s43018-024-00877-z","url":null,"abstract":"Loss of CDKN2A is known to drive the progression of several cancers, including esophageal adenocarcinoma (EAC). Genetic analyses of samples of Barrett’s esophagus (EAC precursor condition) show that early loss of CDKN2A delays EAC initiation. Moreover, the concomitant loss of other genes in the same chromosomal locus has different effects depending on context.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 1","pages":"22-23"},"PeriodicalIF":23.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951993","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}
Pub Date : 2025-01-03DOI: 10.1038/s43018-024-00876-0
Piyali Ganguli, Celia C. Basanta, Amelia Acha-Sagredo, Hrvoje Misetic, Maria Armero, Akram Mendez, Aeman Zahra, Ginny Devonshire, Gavin Kelly, Adam Freeman, Mary Green, Emma Nye, Anita Bichisecchi, Paola Bonfanti, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, Manuel Rodriguez-Justo, Jo Spencer, Rebecca C. Fitzgerald, Francesca D. Ciccarelli
CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data. Despite its cancer driver role, CDKN2A loss in BE prevents EAC initiation by counterselecting subsequent TP53 alterations. 9p21 gene co-deletions predict poor patient survival in EAC but not BE through context-dependent effects on cell cycle, oxidative phosphorylation and interferon response. Immune quantifications using bulk transcriptome, RNAscope and high-dimensional tissue imaging showed that IFNE loss reduces immune infiltration in BE, but not EAC. Mechanistically, CDKN2A loss suppresses the maintenance of squamous epithelium, contributing to a more aggressive phenotype. Our study demonstrates context-dependent roles of cancer genes during disease evolution, with consequences for cancer detection and patient management. Ganguli et al. show that CDKN2A loss in Barrett’s esophagus prevents esophageal adenocarcinoma initiation by counterselecting subsequent TP53 loss and report context-dependent effects of 9p21 gene co-deletions on disease progression.
{"title":"Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer","authors":"Piyali Ganguli, Celia C. Basanta, Amelia Acha-Sagredo, Hrvoje Misetic, Maria Armero, Akram Mendez, Aeman Zahra, Ginny Devonshire, Gavin Kelly, Adam Freeman, Mary Green, Emma Nye, Anita Bichisecchi, Paola Bonfanti, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, Manuel Rodriguez-Justo, Jo Spencer, Rebecca C. Fitzgerald, Francesca D. Ciccarelli","doi":"10.1038/s43018-024-00876-0","DOIUrl":"10.1038/s43018-024-00876-0","url":null,"abstract":"CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data. Despite its cancer driver role, CDKN2A loss in BE prevents EAC initiation by counterselecting subsequent TP53 alterations. 9p21 gene co-deletions predict poor patient survival in EAC but not BE through context-dependent effects on cell cycle, oxidative phosphorylation and interferon response. Immune quantifications using bulk transcriptome, RNAscope and high-dimensional tissue imaging showed that IFNE loss reduces immune infiltration in BE, but not EAC. Mechanistically, CDKN2A loss suppresses the maintenance of squamous epithelium, contributing to a more aggressive phenotype. Our study demonstrates context-dependent roles of cancer genes during disease evolution, with consequences for cancer detection and patient management. Ganguli et al. show that CDKN2A loss in Barrett’s esophagus prevents esophageal adenocarcinoma initiation by counterselecting subsequent TP53 loss and report context-dependent effects of 9p21 gene co-deletions on disease progression.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 1","pages":"158-174"},"PeriodicalIF":23.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927561","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}
Pub Date : 2025-01-03DOI: 10.1038/s43018-024-00882-2
Roberto Würth, Elisa Donato, Laura L. Michel, Massimo Saini, Lisa Becker, Tasneem Cheytan, Daria Doncevic, Tobias Messmer, Ewgenija Gutjahr, Rebecca Weber, Corinna Klein, Hamed Alborzinia, Umut Yildiz, Vanessa Vogel, Mario Hlevnjak, Polina Kozyulina, Sarah-Jane Neuberth, Paul Schwerd-Kleine, Sevinç Jakab, Nicole Pfarr, Arlou Kristina Angeles, Astrid K. Laut, Darja Karpova, Mattia Falcone, Olaf Hardt, Benjamin Theek, Celina V. Wagner, Mirjam Becker, Sabine Wagner, Martina Haselmayr, Anita Schmitt, Carsten Müller-Tidow, Sabine Riethdorf, Klaus Pantel, Marc Zapatka, Holger Sültmann, Carl Herrmann, Verena Thewes, Peter Lichter, Andreas Schneeweiss, Martin R. Sprick, Andreas Trumpp
Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer. Multiomics analysis of CTC-derived organoids along with preclinical modeling with xenografts identified neuregulin 1 (NRG1)–ERBB2 receptor tyrosine kinase 3 (ERBB3/HER3) signaling as a key pathway required for CTC survival, growth and dissemination. Genome-wide CRISPR activation screens revealed that fibroblast growth factor receptor 1 (FGFR1) signaling serves a compensatory function to the NRG1–HER3 axis and rescues NRG1 deficiency in CTCs. Conversely, NRG1–HER3 activation induced resistance to FGFR1 inhibition, whereas combinatorial blockade impaired CTC growth. The dynamic interplay between NRG1–HER3 and FGFR1 signaling reveals the molecular basis of cancer cell plasticity and clinically relevant strategies to target it. Our CTC organoid platform enables the identification and validation of patient-specific vulnerabilities and represents an innovative tool for precision medicine. Trumpp and colleagues develop a method to obtain long-term circulating tumor cell-derived organoids from individuals with metastatic breast cancer and identify the neuregulin 1–HER3 axis as important for organoid growth and a promising therapeutic target.
{"title":"Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1–HER3 signaling","authors":"Roberto Würth, Elisa Donato, Laura L. Michel, Massimo Saini, Lisa Becker, Tasneem Cheytan, Daria Doncevic, Tobias Messmer, Ewgenija Gutjahr, Rebecca Weber, Corinna Klein, Hamed Alborzinia, Umut Yildiz, Vanessa Vogel, Mario Hlevnjak, Polina Kozyulina, Sarah-Jane Neuberth, Paul Schwerd-Kleine, Sevinç Jakab, Nicole Pfarr, Arlou Kristina Angeles, Astrid K. Laut, Darja Karpova, Mattia Falcone, Olaf Hardt, Benjamin Theek, Celina V. Wagner, Mirjam Becker, Sabine Wagner, Martina Haselmayr, Anita Schmitt, Carsten Müller-Tidow, Sabine Riethdorf, Klaus Pantel, Marc Zapatka, Holger Sültmann, Carl Herrmann, Verena Thewes, Peter Lichter, Andreas Schneeweiss, Martin R. Sprick, Andreas Trumpp","doi":"10.1038/s43018-024-00882-2","DOIUrl":"10.1038/s43018-024-00882-2","url":null,"abstract":"Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer. Multiomics analysis of CTC-derived organoids along with preclinical modeling with xenografts identified neuregulin 1 (NRG1)–ERBB2 receptor tyrosine kinase 3 (ERBB3/HER3) signaling as a key pathway required for CTC survival, growth and dissemination. Genome-wide CRISPR activation screens revealed that fibroblast growth factor receptor 1 (FGFR1) signaling serves a compensatory function to the NRG1–HER3 axis and rescues NRG1 deficiency in CTCs. Conversely, NRG1–HER3 activation induced resistance to FGFR1 inhibition, whereas combinatorial blockade impaired CTC growth. The dynamic interplay between NRG1–HER3 and FGFR1 signaling reveals the molecular basis of cancer cell plasticity and clinically relevant strategies to target it. Our CTC organoid platform enables the identification and validation of patient-specific vulnerabilities and represents an innovative tool for precision medicine. Trumpp and colleagues develop a method to obtain long-term circulating tumor cell-derived organoids from individuals with metastatic breast cancer and identify the neuregulin 1–HER3 axis as important for organoid growth and a promising therapeutic target.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 1","pages":"67-85"},"PeriodicalIF":23.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927543","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}
Pub Date : 2025-01-02DOI: 10.1038/s43018-024-00880-4
Richa Shah, Nader Mounir Hanna, Ching Ee Loo, Michael David, Allini Mafra, Hanna Fink, Ethna McFerran, Montse Garcia, Robabeh Ghodssighassemabadi, Suryakanta Acharya, Jean Niyibaga, Oliver Langselius, Clara Frick, Nwamaka Lasebikan, Jerome Vignat, Julia Steinberg, Suzanne Hughes, Colleen Elizabeth Kircher, Catherine Lindsay Goldie, Sam Egger, Richard Sullivan, Ophira Ginsburg, Freddie Bray, Michael Caruana, Harriet Hui, André Michel Ilbawi, Karen Canfell, Isabelle Soerjomataram
The coronavirus disease 2019 pandemic substantially impacted the delivery of cancer services and programs. Here we reviewed and synthesized the global scale and impact of pandemic-related delays and disruptions on cancer services, including diagnosis, diagnostic procedures, screening, treatment and supportive and palliative care. Based on data from 245 articles in 46 countries, we observed declines in the number of cancer screening participation (39.0%), diagnoses (23.0%), diagnostic procedures (24.0%) and treatment (28.0%), ranging from a 15.0% decline for radiotherapy to a 35.0% decline for systemic treatment during the pandemic compared to during the prepandemic period. Medium-human development index (HDI) category countries experienced greater reductions than high- and very-high-HDI countries. Missing data from low-HDI countries emphasize the need for increased investments in cancer surveillance and research in these settings. PROSPERO registration: CRD42022301816 Shah et al. conducted a systematic review and meta-analysis of the impact of COVID-19 pandemic-related disruptions to cancer healthcare services and reported reduced cancer screening, diagnosis and treatment of patients.
{"title":"The global impact of the COVID-19 pandemic on delays and disruptions in cancer care services: a systematic review and meta-analysis","authors":"Richa Shah, Nader Mounir Hanna, Ching Ee Loo, Michael David, Allini Mafra, Hanna Fink, Ethna McFerran, Montse Garcia, Robabeh Ghodssighassemabadi, Suryakanta Acharya, Jean Niyibaga, Oliver Langselius, Clara Frick, Nwamaka Lasebikan, Jerome Vignat, Julia Steinberg, Suzanne Hughes, Colleen Elizabeth Kircher, Catherine Lindsay Goldie, Sam Egger, Richard Sullivan, Ophira Ginsburg, Freddie Bray, Michael Caruana, Harriet Hui, André Michel Ilbawi, Karen Canfell, Isabelle Soerjomataram","doi":"10.1038/s43018-024-00880-4","DOIUrl":"10.1038/s43018-024-00880-4","url":null,"abstract":"The coronavirus disease 2019 pandemic substantially impacted the delivery of cancer services and programs. Here we reviewed and synthesized the global scale and impact of pandemic-related delays and disruptions on cancer services, including diagnosis, diagnostic procedures, screening, treatment and supportive and palliative care. Based on data from 245 articles in 46 countries, we observed declines in the number of cancer screening participation (39.0%), diagnoses (23.0%), diagnostic procedures (24.0%) and treatment (28.0%), ranging from a 15.0% decline for radiotherapy to a 35.0% decline for systemic treatment during the pandemic compared to during the prepandemic period. Medium-human development index (HDI) category countries experienced greater reductions than high- and very-high-HDI countries. Missing data from low-HDI countries emphasize the need for increased investments in cancer surveillance and research in these settings. PROSPERO registration: CRD42022301816 Shah et al. conducted a systematic review and meta-analysis of the impact of COVID-19 pandemic-related disruptions to cancer healthcare services and reported reduced cancer screening, diagnosis and treatment of patients.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 1","pages":"194-204"},"PeriodicalIF":23.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922109","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}
Pub Date : 2025-01-02DOI: 10.1038/s43018-024-00872-4
Brian Keith, Danny R. Welch, Nishtha Agarwal, Caroline Blair, Ifeanyi Beverly Chukwudozie, Lalita A. Shevde, Lawrence H. Boise, Kerry L. Burnstein, Toni M. Antalis, Kathleen L. O’Connor, Sorab N. Dalal, Sheridan Ellis, Harikrishna Nakshatri
Training the next generation of cancer researchers is essential for the cancer research enterprise. However, training programs and methods to evaluate their effectiveness vary greatly across the USA and other countries. Here we discuss strategies to enhance cancer education and processes by which training may be standardized.
{"title":"Challenges and opportunities in training cancer researchers","authors":"Brian Keith, Danny R. Welch, Nishtha Agarwal, Caroline Blair, Ifeanyi Beverly Chukwudozie, Lalita A. Shevde, Lawrence H. Boise, Kerry L. Burnstein, Toni M. Antalis, Kathleen L. O’Connor, Sorab N. Dalal, Sheridan Ellis, Harikrishna Nakshatri","doi":"10.1038/s43018-024-00872-4","DOIUrl":"10.1038/s43018-024-00872-4","url":null,"abstract":"Training the next generation of cancer researchers is essential for the cancer research enterprise. However, training programs and methods to evaluate their effectiveness vary greatly across the USA and other countries. Here we discuss strategies to enhance cancer education and processes by which training may be standardized.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 2","pages":"223-225"},"PeriodicalIF":23.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922103","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}
Pub Date : 2024-12-20DOI: 10.1038/s43018-024-00858-2
Jiaxu Zhao, Rui Zeng, Xiaohui Li, Ying Lu, Zuoyun Wang, Haibao Peng, Hao Chen, Minjie Fu, Ye Zhang, Yang Huang, Wenhan Chen, Xin Wang, Yun Guan, Wei Han, Ruofan Huang, Chengjun Yao, Zhiyong Qin, Lingchao Chen, Liang Chen, Xue Feng, Hanting Yang, Patrícia M. R. Pereira, Xuemei Tong, Bin Li, Qiangqiang Zhang, Yudan Chi
The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression. Mechanically, we find that dura-derived LM-associated macrophages (dLAMs) migrate into the CSF in a matrix metalloproteinase 14 (MMP14)-dependent manner. Furthermore, we identify that dLAMs critically require the presence of secreted phosphoprotein 1 (SPP1) in cancer cells for their recruitment, fostering an immunosuppressed microenvironment characterized by T cell exhaustion and inactivation. Conversely, inhibition of the SPP1–MMP14 axis can impede macrophages from bypassing the border barrier, prevent cancer cell growth and improve survival in LM mouse models. Our findings reveal an unexpectedly private source of innate immunity within the meningeal space, shed light on CSF barrier dysfunction dynamics and supply potential targets of clinical immunotherapy. Zhao et al. find that a macrophage subset migrates from the dura matter to reshape the cerebrospinal fluid microenvironment and promote metastasis and show that the secreted phosphoprotein 1–matrix metallopeptidase 14 axis can be targeted to inhibit this.
{"title":"Dura immunity configures leptomeningeal metastasis immunosuppression for cerebrospinal fluid barrier invasion","authors":"Jiaxu Zhao, Rui Zeng, Xiaohui Li, Ying Lu, Zuoyun Wang, Haibao Peng, Hao Chen, Minjie Fu, Ye Zhang, Yang Huang, Wenhan Chen, Xin Wang, Yun Guan, Wei Han, Ruofan Huang, Chengjun Yao, Zhiyong Qin, Lingchao Chen, Liang Chen, Xue Feng, Hanting Yang, Patrícia M. R. Pereira, Xuemei Tong, Bin Li, Qiangqiang Zhang, Yudan Chi","doi":"10.1038/s43018-024-00858-2","DOIUrl":"10.1038/s43018-024-00858-2","url":null,"abstract":"The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression. Mechanically, we find that dura-derived LM-associated macrophages (dLAMs) migrate into the CSF in a matrix metalloproteinase 14 (MMP14)-dependent manner. Furthermore, we identify that dLAMs critically require the presence of secreted phosphoprotein 1 (SPP1) in cancer cells for their recruitment, fostering an immunosuppressed microenvironment characterized by T cell exhaustion and inactivation. Conversely, inhibition of the SPP1–MMP14 axis can impede macrophages from bypassing the border barrier, prevent cancer cell growth and improve survival in LM mouse models. Our findings reveal an unexpectedly private source of innate immunity within the meningeal space, shed light on CSF barrier dysfunction dynamics and supply potential targets of clinical immunotherapy. Zhao et al. find that a macrophage subset migrates from the dura matter to reshape the cerebrospinal fluid microenvironment and promote metastasis and show that the secreted phosphoprotein 1–matrix metallopeptidase 14 axis can be targeted to inhibit this.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1940-1961"},"PeriodicalIF":23.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870516","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}
Pub Date : 2024-12-20DOI: 10.1038/s43018-024-00859-1
Michael Kilian, Francisco J. Quintana
Leptomeningeal metastases of solid tumors are associated with poor prognosis, limited treatment options and unclear immunosurveillance mechanisms. Dura-derived immunosuppressive macrophages are now shown to migrate to the cerebrospinal fluid, limiting anti-tumor CD8+ T cell responses in models of leptomeningeal metastasis.
{"title":"Immunosuppressive dura-derived macrophages in leptomeningeal metastasis","authors":"Michael Kilian, Francisco J. Quintana","doi":"10.1038/s43018-024-00859-1","DOIUrl":"10.1038/s43018-024-00859-1","url":null,"abstract":"Leptomeningeal metastases of solid tumors are associated with poor prognosis, limited treatment options and unclear immunosurveillance mechanisms. Dura-derived immunosuppressive macrophages are now shown to migrate to the cerebrospinal fluid, limiting anti-tumor CD8+ T cell responses in models of leptomeningeal metastasis.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1791-1792"},"PeriodicalIF":23.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870527","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}
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