Pub Date : 2024-02-14DOI: 10.1038/s43018-024-00729-w
Evanthia.T. Roussos Torres, Won J. Ho, Ludmila Danilova, Joseph A. Tandurella, James Leatherman, Christine Rafie, Chenguang Wang, Adam Brufsky, Patricia LoRusso, Vincent Chung, Yuan Yuan, Melinda Downs, Ashley O’Connor, Sarah M. Shin, Alexei Hernandez, Elizabeth L. Engle, Richard Piekarz, Howard Streicher, Zahra Talebi, Michelle A. Rudek, Qingfeng Zhu, Robert A. Anders, Ashley Cimino-Mathews, Elana J. Fertig, Elizabeth M. Jaffee, Vered Stearns, Roisin M. Connolly
We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial. Roussos-Torres and colleagues perform a phase Ib clinical trial of entinostat, nivolumab and ipilimumab in individuals with advanced HER2-negative breast cancer, report on safety and response and characterize the immune-modulatory effects.
{"title":"Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial","authors":"Evanthia.T. Roussos Torres, Won J. Ho, Ludmila Danilova, Joseph A. Tandurella, James Leatherman, Christine Rafie, Chenguang Wang, Adam Brufsky, Patricia LoRusso, Vincent Chung, Yuan Yuan, Melinda Downs, Ashley O’Connor, Sarah M. Shin, Alexei Hernandez, Elizabeth L. Engle, Richard Piekarz, Howard Streicher, Zahra Talebi, Michelle A. Rudek, Qingfeng Zhu, Robert A. Anders, Ashley Cimino-Mathews, Elana J. Fertig, Elizabeth M. Jaffee, Vered Stearns, Roisin M. Connolly","doi":"10.1038/s43018-024-00729-w","DOIUrl":"10.1038/s43018-024-00729-w","url":null,"abstract":"We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial. Roussos-Torres and colleagues perform a phase Ib clinical trial of entinostat, nivolumab and ipilimumab in individuals with advanced HER2-negative breast cancer, report on safety and response and characterize the immune-modulatory effects.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":23.5,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735662","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 : 2024-02-14DOI: 10.1038/s43018-023-00714-9
Our study reveals that the LGR4–Wnt signaling pathway dictates both ferroptosis and stemness traits to confer drug resistance to tumor cells. We thus generated a monoclonal antibody against LGR4 that blocks LGR4–Wnt signaling and sensitizes chemotherapy-resistant colorectal cancer tumors via selective promotion of ferroptosis.
{"title":"Targeting LGR4–Wnt activates ferroptosis and reverses drug resistance in colorectal cancer","authors":"","doi":"10.1038/s43018-023-00714-9","DOIUrl":"10.1038/s43018-023-00714-9","url":null,"abstract":"Our study reveals that the LGR4–Wnt signaling pathway dictates both ferroptosis and stemness traits to confer drug resistance to tumor cells. We thus generated a monoclonal antibody against LGR4 that blocks LGR4–Wnt signaling and sensitizes chemotherapy-resistant colorectal cancer tumors via selective promotion of ferroptosis.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735663","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 : 2024-02-13DOI: 10.1038/s43018-024-00727-y
Christopher J. Bergin, Aïcha Zouggar, Amanda Mendes da Silva, Tanguy Fenouil, Joshua R. Haebe, Angelique N. Masibag, Gautam Agrawal, Muhammad S. Shah, Tamara Sandouka, Mario Tiberi, Rebecca C. Auer, Michele Ardolino, Yannick D. Benoit
Cancer stem cells (CSCs), functionally characterized by self-renewal and tumor-initiating activity, contribute to decreased tumor immunogenicity, while fostering tumor growth and metastasis. Targeting G9a histone methyltransferase (HMTase) effectively blocks CSC functions in colorectal tumors by altering pluripotent-like molecular networks; however, existing molecules directly targeting G9a HMTase activity failed to reach clinical stages due to safety concerns. Using a stem cell-based phenotypic drug-screening pipeline, we identified the dopamine transporter (DAT) antagonist vanoxerine, a compound with previously demonstrated clinical safety, as a cancer-specific downregulator of G9a expression. Here we show that gene silencing and chemical antagonism of DAT impede colorectal CSC functions by repressing G9a expression. Antagonizing DAT also enhanced tumor lymphocytic infiltration by activating endogenous transposable elements and type-I interferon response. Our study unveils the direct implication of the DAT–G9a axis in the maintenance of CSC populations and an approach to improve antitumor immune response in colon tumors. Benoit and colleagues identify the dopamine transporter antagonist vanoxerine as a suppressor of G9a methyltransferase and show that treatment leads to cancer stem cell suppression and restoration of an immunoresponsive tumor microenvironment in CRC.
{"title":"The dopamine transporter antagonist vanoxerine inhibits G9a and suppresses cancer stem cell functions in colon tumors","authors":"Christopher J. Bergin, Aïcha Zouggar, Amanda Mendes da Silva, Tanguy Fenouil, Joshua R. Haebe, Angelique N. Masibag, Gautam Agrawal, Muhammad S. Shah, Tamara Sandouka, Mario Tiberi, Rebecca C. Auer, Michele Ardolino, Yannick D. Benoit","doi":"10.1038/s43018-024-00727-y","DOIUrl":"10.1038/s43018-024-00727-y","url":null,"abstract":"Cancer stem cells (CSCs), functionally characterized by self-renewal and tumor-initiating activity, contribute to decreased tumor immunogenicity, while fostering tumor growth and metastasis. Targeting G9a histone methyltransferase (HMTase) effectively blocks CSC functions in colorectal tumors by altering pluripotent-like molecular networks; however, existing molecules directly targeting G9a HMTase activity failed to reach clinical stages due to safety concerns. Using a stem cell-based phenotypic drug-screening pipeline, we identified the dopamine transporter (DAT) antagonist vanoxerine, a compound with previously demonstrated clinical safety, as a cancer-specific downregulator of G9a expression. Here we show that gene silencing and chemical antagonism of DAT impede colorectal CSC functions by repressing G9a expression. Antagonizing DAT also enhanced tumor lymphocytic infiltration by activating endogenous transposable elements and type-I interferon response. Our study unveils the direct implication of the DAT–G9a axis in the maintenance of CSC populations and an approach to improve antitumor immune response in colon tumors. Benoit and colleagues identify the dopamine transporter antagonist vanoxerine as a suppressor of G9a methyltransferase and show that treatment leads to cancer stem cell suppression and restoration of an immunoresponsive tumor microenvironment in CRC.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730072","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 : 2024-02-13DOI: 10.1038/s43018-024-00726-z
Christina L. Roland, Elise F. Nassif Haddad, Emily Z. Keung, Wei-Lien Wang, Alexander J. Lazar, Heather Lin, Manoj Chelvanambi, Edwin R. Parra, Khalida Wani, B. Ashleigh Guadagnolo, Andrew J. Bishop, Elizabeth M. Burton, Kelly K. Hunt, Keila E. Torres, Barry W. Feig, Christopher P. Scally, Valerae O. Lewis, Justin E. Bird, Ravin Ratan, Dejka Araujo, M. Alexandra Zarzour, Shreyaskumar Patel, Robert Benjamin, Anthony P. Conley, J. Andrew Livingston, Vinod Ravi, Hussein A. Tawbi, Patrick P. Lin, Bryan S. Moon, Robert L. Satcher, Bilal Mujtaba, Russell G. Witt, Raymond S. Traweek, Brandon Cope, Rossana Lazcano, Chia-Chin Wu, Xiao Zhou, Mohammad M. Mohammad, Randy A. Chu, Jianhua Zhang, Ashish Damania, Pranoti Sahasrabhojane, Taylor Tate, Kate Callahan, Sa Nguyen, Davis Ingram, Rohini Morey, Shadarra Crosby, Grace Mathew, Sheila Duncan, Cibelle F. Lima, Jean-Yves Blay, Wolf Herman Fridman, Kenna Shaw, Ignacio Wistuba, Andrew Futreal, Nadim Ajami, Jennifer A. Wargo, Neeta Somaiah
Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS. Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.
{"title":"A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma","authors":"Christina L. Roland, Elise F. Nassif Haddad, Emily Z. Keung, Wei-Lien Wang, Alexander J. Lazar, Heather Lin, Manoj Chelvanambi, Edwin R. Parra, Khalida Wani, B. Ashleigh Guadagnolo, Andrew J. Bishop, Elizabeth M. Burton, Kelly K. Hunt, Keila E. Torres, Barry W. Feig, Christopher P. Scally, Valerae O. Lewis, Justin E. Bird, Ravin Ratan, Dejka Araujo, M. Alexandra Zarzour, Shreyaskumar Patel, Robert Benjamin, Anthony P. Conley, J. Andrew Livingston, Vinod Ravi, Hussein A. Tawbi, Patrick P. Lin, Bryan S. Moon, Robert L. Satcher, Bilal Mujtaba, Russell G. Witt, Raymond S. Traweek, Brandon Cope, Rossana Lazcano, Chia-Chin Wu, Xiao Zhou, Mohammad M. Mohammad, Randy A. Chu, Jianhua Zhang, Ashish Damania, Pranoti Sahasrabhojane, Taylor Tate, Kate Callahan, Sa Nguyen, Davis Ingram, Rohini Morey, Shadarra Crosby, Grace Mathew, Sheila Duncan, Cibelle F. Lima, Jean-Yves Blay, Wolf Herman Fridman, Kenna Shaw, Ignacio Wistuba, Andrew Futreal, Nadim Ajami, Jennifer A. Wargo, Neeta Somaiah","doi":"10.1038/s43018-024-00726-z","DOIUrl":"10.1038/s43018-024-00726-z","url":null,"abstract":"Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS. Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730070","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 : 2024-02-13DOI: 10.1038/s43018-024-00723-2
Winnie Chen, Ian Maze
Self-renewing cancer stem cells drive tumor initiation and progression and represent a major target for therapeutic development. A study now shows that vanoxerine, a dopamine transporter antagonist, precisely inhibits this cell population in colorectal cancer, which leads to attenuation of tumor initiation and increased infiltration by immune cells.
{"title":"Repurposing the dopamine transporter antagonist vanoxerine to treat colorectal cancer","authors":"Winnie Chen, Ian Maze","doi":"10.1038/s43018-024-00723-2","DOIUrl":"10.1038/s43018-024-00723-2","url":null,"abstract":"Self-renewing cancer stem cells drive tumor initiation and progression and represent a major target for therapeutic development. A study now shows that vanoxerine, a dopamine transporter antagonist, precisely inhibits this cell population in colorectal cancer, which leads to attenuation of tumor initiation and increased infiltration by immune cells.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730071","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 : 2024-02-12DOI: 10.1038/s43018-023-00705-w
Using CRISPR–Cas9 screens, we found that cancer-cell-intrinsic loss of Pip4k2c conferred liver-metastatic organotropism in melanoma through hypersensitization to insulin-mediated PI3K–AKT signaling via co-optation of distinct hepatic metabolic cues. Additionally, we showed that combinatorial therapies that abolished physiological and drug-induced changes in glucose and insulin levels specifically reduced liver metastasis.
{"title":"Melanoma leverages local cues to promote liver-specific metastasis","authors":"","doi":"10.1038/s43018-023-00705-w","DOIUrl":"10.1038/s43018-023-00705-w","url":null,"abstract":"Using CRISPR–Cas9 screens, we found that cancer-cell-intrinsic loss of Pip4k2c conferred liver-metastatic organotropism in melanoma through hypersensitization to insulin-mediated PI3K–AKT signaling via co-optation of distinct hepatic metabolic cues. Additionally, we showed that combinatorial therapies that abolished physiological and drug-induced changes in glucose and insulin levels specifically reduced liver metastasis.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723347","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 : 2024-02-12DOI: 10.1038/s43018-024-00725-0
Yi-Zhou Jiang, Ding Ma, Xi Jin, Yi Xiao, Ying Yu, Jinxiu Shi, Yi-Fan Zhou, Tong Fu, Cai-Jin Lin, Lei-Jie Dai, Cheng-Lin Liu, Shen Zhao, Guan-Hua Su, Wanwan Hou, Yaqing Liu, Qingwang Chen, Jingcheng Yang, Naixin Zhang, Wen-Juan Zhang, Wei Liu, Weigang Ge, Wen-Tao Yang, Chao You, Yajia Gu, Virginia Kaklamani, François Bertucci, Claire Verschraegen, Anneleen Daemen, Nakul M. Shah, Ting Wang, Tiannan Guo, Leming Shi, Charles M. Perou, Yuanting Zheng, Wei Huang, Zhi-Ming Shao
Molecular profiling guides precision treatment of breast cancer; however, Asian patients are underrepresented in publicly available large-scale studies. We established a comprehensive multiomics cohort of 773 Chinese patients with breast cancer and systematically analyzed their genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology characteristics. Here we show that compared to breast cancers in white individuals, Asian individuals had more targetable AKT1 mutations. Integrated analysis revealed a higher proportion of HER2-enriched subtype and correspondingly more frequent ERBB2 amplification and higher HER2 protein abundance in the Chinese HR+HER2+ cohort, stressing anti-HER2 therapy for these individuals. Furthermore, comprehensive metabolomic and proteomic analyses revealed ferroptosis as a potential therapeutic target for basal-like tumors. The integration of clinical, transcriptomic, metabolomic, radiomic and pathological features allowed for efficient stratification of patients into groups with varying recurrence risks. Our study provides a public resource and new insights into the biology and ancestry specificity of breast cancer in the Asian population, offering potential for further precision treatment approaches. Shao and colleagues present a multiomic analysis of breast tumor samples from Chinese patients, consisting of genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology data.
{"title":"Integrated multiomic profiling of breast cancer in the Chinese population reveals patient stratification and therapeutic vulnerabilities","authors":"Yi-Zhou Jiang, Ding Ma, Xi Jin, Yi Xiao, Ying Yu, Jinxiu Shi, Yi-Fan Zhou, Tong Fu, Cai-Jin Lin, Lei-Jie Dai, Cheng-Lin Liu, Shen Zhao, Guan-Hua Su, Wanwan Hou, Yaqing Liu, Qingwang Chen, Jingcheng Yang, Naixin Zhang, Wen-Juan Zhang, Wei Liu, Weigang Ge, Wen-Tao Yang, Chao You, Yajia Gu, Virginia Kaklamani, François Bertucci, Claire Verschraegen, Anneleen Daemen, Nakul M. Shah, Ting Wang, Tiannan Guo, Leming Shi, Charles M. Perou, Yuanting Zheng, Wei Huang, Zhi-Ming Shao","doi":"10.1038/s43018-024-00725-0","DOIUrl":"10.1038/s43018-024-00725-0","url":null,"abstract":"Molecular profiling guides precision treatment of breast cancer; however, Asian patients are underrepresented in publicly available large-scale studies. We established a comprehensive multiomics cohort of 773 Chinese patients with breast cancer and systematically analyzed their genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology characteristics. Here we show that compared to breast cancers in white individuals, Asian individuals had more targetable AKT1 mutations. Integrated analysis revealed a higher proportion of HER2-enriched subtype and correspondingly more frequent ERBB2 amplification and higher HER2 protein abundance in the Chinese HR+HER2+ cohort, stressing anti-HER2 therapy for these individuals. Furthermore, comprehensive metabolomic and proteomic analyses revealed ferroptosis as a potential therapeutic target for basal-like tumors. The integration of clinical, transcriptomic, metabolomic, radiomic and pathological features allowed for efficient stratification of patients into groups with varying recurrence risks. Our study provides a public resource and new insights into the biology and ancestry specificity of breast cancer in the Asian population, offering potential for further precision treatment approaches. Shao and colleagues present a multiomic analysis of breast tumor samples from Chinese patients, consisting of genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology data.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723346","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 : 2024-02-09DOI: 10.1038/s43018-023-00722-9
Mitochondrial DNA mutations are present in over 50% of all cancers, and truncating mutations in several genes encoding components of complex I of the respiratory chain are most recurrent. We found that these mutations are a source of Warburg-like metabolic shifts that promote a pro-inflammatory immunological state, enhancing sensitivity to checkpoint blockade.
{"title":"Mitochondrial DNA mutation enhances sensitivity to immunotherapy in melanoma","authors":"","doi":"10.1038/s43018-023-00722-9","DOIUrl":"10.1038/s43018-023-00722-9","url":null,"abstract":"Mitochondrial DNA mutations are present in over 50% of all cancers, and truncating mutations in several genes encoding components of complex I of the respiratory chain are most recurrent. We found that these mutations are a source of Warburg-like metabolic shifts that promote a pro-inflammatory immunological state, enhancing sensitivity to checkpoint blockade.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712648","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 : 2024-02-08DOI: 10.1038/s43018-023-00713-w
Senescent cancer cells, which are characteristically present in tumors after genotoxic therapies, upregulate the immune checkpoint ligand programmed cell death 1 ligand 2 (PD-L2). We show that genetic or pharmacological ablation of PD-L2 prevents the accumulation of intratumoral senescent cells, reducing the recruitment of immunosuppressive myeloid cells and facilitating tumor clearance by T cells.
衰老癌细胞是基因毒性疗法后肿瘤中出现的特征性细胞，它们会上调免疫检查点配体程序性细胞死亡1配体2（PD-L2）。我们的研究表明，通过基因或药物消减 PD-L2 可以防止瘤内衰老细胞的聚集，减少免疫抑制性髓系细胞的招募，促进 T 细胞清除肿瘤。
{"title":"PD-L2 expression in senescent cancer cells limits tumor clearance after chemotherapy","authors":"","doi":"10.1038/s43018-023-00713-w","DOIUrl":"10.1038/s43018-023-00713-w","url":null,"abstract":"Senescent cancer cells, which are characteristically present in tumors after genotoxic therapies, upregulate the immune checkpoint ligand programmed cell death 1 ligand 2 (PD-L2). We show that genetic or pharmacological ablation of PD-L2 prevents the accumulation of intratumoral senescent cells, reducing the recruitment of immunosuppressive myeloid cells and facilitating tumor clearance by T cells.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707280","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 : 2024-02-06DOI: 10.1038/s43018-023-00717-6
Macha Nikolski, Eivind Hovig, Fatima Al-Shahrour, Niklas Blomberg, Serena Scollen, Alfonso Valencia, Gary Saunders
Gold-standard cancer data management is pivotal to enable precision medicine for European citizens. Achieving this goal relies on key elements: adopting standardized data formats, ensuring robust data privacy, educating professionals about the infrastructure’s benefits and leveraging cutting-edge technologies to transform cancer care.
{"title":"Roadmap for a European cancer data management and precision medicine infrastructure","authors":"Macha Nikolski, Eivind Hovig, Fatima Al-Shahrour, Niklas Blomberg, Serena Scollen, Alfonso Valencia, Gary Saunders","doi":"10.1038/s43018-023-00717-6","DOIUrl":"10.1038/s43018-023-00717-6","url":null,"abstract":"Gold-standard cancer data management is pivotal to enable precision medicine for European citizens. Achieving this goal relies on key elements: adopting standardized data formats, ensuring robust data privacy, educating professionals about the infrastructure’s benefits and leveraging cutting-edge technologies to transform cancer care.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":null,"pages":null},"PeriodicalIF":22.7,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697925","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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