Augusto Faria Andrade, Romain Sigaud, Evan Puligandla, Bridget Liu, Elham Karimi, Alva Annett, Morteza Rezanejad, Wajih Jawhar, Robert Taylor, Yi Cao, Simone Schmid, Florian Selt, Pablo Hernáiz Driever, Svea Horn, Philipp Sievers, Marco Prinz, Markus Glatzel, Christian Mawrin, Christian Hartmann, Camelia-Maria Monoranu, Liza Konnikova, Felix Sahm, Stefan M. Pfister, Olaf Witt, David T. W. Jones, Arend Koch, Claudia L. Kleinman, David Capper, Logan Walsh, Nada Jabado, Till Milde
{"title":"儿童低级别胶质瘤中mapk激活的免疫抑制髓细胞群的空间图","authors":"Augusto Faria Andrade, Romain Sigaud, Evan Puligandla, Bridget Liu, Elham Karimi, Alva Annett, Morteza Rezanejad, Wajih Jawhar, Robert Taylor, Yi Cao, Simone Schmid, Florian Selt, Pablo Hernáiz Driever, Svea Horn, Philipp Sievers, Marco Prinz, Markus Glatzel, Christian Mawrin, Christian Hartmann, Camelia-Maria Monoranu, Liza Konnikova, Felix Sahm, Stefan M. Pfister, Olaf Witt, David T. W. Jones, Arend Koch, Claudia L. Kleinman, David Capper, Logan Walsh, Nada Jabado, Till Milde","doi":"10.1038/s41590-025-02268-7","DOIUrl":null,"url":null,"abstract":"Pediatric low-grade gliomas (pLGGs) are mitogen-activated protein kinase (MAPK) pathway-activated brain tumors prevalent in children and are associated with morbidity despite favorable survival. Here using imaging mass cytometry, we spatially characterized at the single-cell level the tumor microenvironment (TME) of 120 pLGG cases, considering age, molecular drivers, brain location and tumor subtype. Our analysis identified myeloid cells—including resident microglia and bone marrow-derived macrophages—as the predominant immune population in the TME, particularly in optic pathway tumors. Additionally, we discovered an immune signature predictive of progression-free survival. Spatial analysis identified specific cellular interactions, notably myeloid–myeloid contacts and macrophage-enriched regions harboring MAPK-activated, TIM-3+ myeloid cells, suggesting an immunosuppressive TME. Our study provides a comprehensive resource on the immune landscape of these pLGGs and underscores the immunosuppressive role of diverse myeloid infiltrates. These findings also indicate that combining TIM-3 blockade with MAPK inhibition might be a promising therapeutic strategy to target both the TME and oncogenic MAPK activation in pLGG tumors. Here the authors spatially map human pediatric low-grade gliomas using imaging mass cytometry, focusing on immunosuppressive myeloid cell populations and their functionality in tumor–immune interactions and tumor progression.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 10","pages":"1794-1806"},"PeriodicalIF":27.6000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma\",\"authors\":\"Augusto Faria Andrade, Romain Sigaud, Evan Puligandla, Bridget Liu, Elham Karimi, Alva Annett, Morteza Rezanejad, Wajih Jawhar, Robert Taylor, Yi Cao, Simone Schmid, Florian Selt, Pablo Hernáiz Driever, Svea Horn, Philipp Sievers, Marco Prinz, Markus Glatzel, Christian Mawrin, Christian Hartmann, Camelia-Maria Monoranu, Liza Konnikova, Felix Sahm, Stefan M. Pfister, Olaf Witt, David T. W. Jones, Arend Koch, Claudia L. Kleinman, David Capper, Logan Walsh, Nada Jabado, Till Milde\",\"doi\":\"10.1038/s41590-025-02268-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Pediatric low-grade gliomas (pLGGs) are mitogen-activated protein kinase (MAPK) pathway-activated brain tumors prevalent in children and are associated with morbidity despite favorable survival. Here using imaging mass cytometry, we spatially characterized at the single-cell level the tumor microenvironment (TME) of 120 pLGG cases, considering age, molecular drivers, brain location and tumor subtype. Our analysis identified myeloid cells—including resident microglia and bone marrow-derived macrophages—as the predominant immune population in the TME, particularly in optic pathway tumors. Additionally, we discovered an immune signature predictive of progression-free survival. Spatial analysis identified specific cellular interactions, notably myeloid–myeloid contacts and macrophage-enriched regions harboring MAPK-activated, TIM-3+ myeloid cells, suggesting an immunosuppressive TME. Our study provides a comprehensive resource on the immune landscape of these pLGGs and underscores the immunosuppressive role of diverse myeloid infiltrates. These findings also indicate that combining TIM-3 blockade with MAPK inhibition might be a promising therapeutic strategy to target both the TME and oncogenic MAPK activation in pLGG tumors. Here the authors spatially map human pediatric low-grade gliomas using imaging mass cytometry, focusing on immunosuppressive myeloid cell populations and their functionality in tumor–immune interactions and tumor progression.\",\"PeriodicalId\":19032,\"journal\":{\"name\":\"Nature Immunology\",\"volume\":\"26 10\",\"pages\":\"1794-1806\"},\"PeriodicalIF\":27.6000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41590-025-02268-7\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41590-025-02268-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma
Pediatric low-grade gliomas (pLGGs) are mitogen-activated protein kinase (MAPK) pathway-activated brain tumors prevalent in children and are associated with morbidity despite favorable survival. Here using imaging mass cytometry, we spatially characterized at the single-cell level the tumor microenvironment (TME) of 120 pLGG cases, considering age, molecular drivers, brain location and tumor subtype. Our analysis identified myeloid cells—including resident microglia and bone marrow-derived macrophages—as the predominant immune population in the TME, particularly in optic pathway tumors. Additionally, we discovered an immune signature predictive of progression-free survival. Spatial analysis identified specific cellular interactions, notably myeloid–myeloid contacts and macrophage-enriched regions harboring MAPK-activated, TIM-3+ myeloid cells, suggesting an immunosuppressive TME. Our study provides a comprehensive resource on the immune landscape of these pLGGs and underscores the immunosuppressive role of diverse myeloid infiltrates. These findings also indicate that combining TIM-3 blockade with MAPK inhibition might be a promising therapeutic strategy to target both the TME and oncogenic MAPK activation in pLGG tumors. Here the authors spatially map human pediatric low-grade gliomas using imaging mass cytometry, focusing on immunosuppressive myeloid cell populations and their functionality in tumor–immune interactions and tumor progression.
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.