Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation
Background While major advances have been made in improving the quality of life and survival of children with most forms of medulloblastoma (MB), those with MYC-driven tumors (Grp3-MB) still suffer significant morbidity and mortality. There is an urgent need to explore multimodal therapeutic regimen...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-01-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/1/e005871.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832582776395661312 |
|---|---|
| author | Arndt Borkhardt Nan Qin Stephen T Keir Darell D Bigner Allison Cole Matthias Wölfl Viktoria Marquardt Johanna Theruvath David Pauck Daniel Picard Lena Blümel Mara Maue Jasmin Bartl Ulvi Ahmadov Maike Langini Frauke-Dorothee Meyer Joselyn Cruz-Cruz Claus M Graef Till Milde Olaf Witt Anat Erdreich-Epstein Gabriel Leprivier Ulf Kahlert Anja Stefanski Kai Stühler Julia Hauer Thomas Beez Christiane B Knobbe-Thomsen Ute Fischer Jörg Felsberg Finn K Hansen Rajeev Vibhakar Sujatha Venkatraman Samuel H Cheshier Guido Reifenberger Thomas Kurz Marc Remke Siddhartha Mitra |
| author_facet | Arndt Borkhardt Nan Qin Stephen T Keir Darell D Bigner Allison Cole Matthias Wölfl Viktoria Marquardt Johanna Theruvath David Pauck Daniel Picard Lena Blümel Mara Maue Jasmin Bartl Ulvi Ahmadov Maike Langini Frauke-Dorothee Meyer Joselyn Cruz-Cruz Claus M Graef Till Milde Olaf Witt Anat Erdreich-Epstein Gabriel Leprivier Ulf Kahlert Anja Stefanski Kai Stühler Julia Hauer Thomas Beez Christiane B Knobbe-Thomsen Ute Fischer Jörg Felsberg Finn K Hansen Rajeev Vibhakar Sujatha Venkatraman Samuel H Cheshier Guido Reifenberger Thomas Kurz Marc Remke Siddhartha Mitra |
| author_sort | Arndt Borkhardt |
| collection | DOAJ |
| description | Background While major advances have been made in improving the quality of life and survival of children with most forms of medulloblastoma (MB), those with MYC-driven tumors (Grp3-MB) still suffer significant morbidity and mortality. There is an urgent need to explore multimodal therapeutic regimens which are effective and safe for children. Large-scale studies have revealed abnormal cancer epigenomes caused by mutations and structural alterations of chromatin modifiers, aberrant DNA methylation, and histone modification signatures. Therefore, targeting epigenetic modifiers for cancer treatment has gained increasing interest, and inhibitors for various epigenetic modulators have been intensively studied in clinical trials. Here, we report a cross-entity, epigenetic drug screen to evaluate therapeutic vulnerabilities in MYC amplified MB, which sensitizes them to macrophage-mediated phagocytosis by targeting the CD47-signal regulatory protein α (SIRPα) innate checkpoint pathway.Methods We performed a primary screen including 78 epigenetic inhibitors and a secondary screen including 20 histone deacetylase inhibitors (HDACi) to compare response profiles in atypical teratoid/rhabdoid tumor (AT/RT, n=11), MB (n=14), and glioblastoma (n=14). This unbiased approach revealed the preferential activity of HDACi in MYC-driven MB. Importantly, the class I selective HDACi, CI-994, showed significant cell viability reduction mediated by induction of apoptosis in MYC-driven MB, with little-to-no activity in non-MYC-driven MB, AT/RT, and glioblastoma in vitro. We tested the combinatorial effect of targeting class I HDACs and the CD47-SIRPa phagocytosis checkpoint pathway using in vitro phagocytosis assays and in vivo orthotopic xenograft models.Results CI-994 displayed antitumoral effects at the primary site and the metastatic compartment in two orthotopic mouse models of MYC-driven MB. Furthermore, RNA sequencing revealed nuclear factor-kB (NF-κB) pathway induction as a response to CI-994 treatment, followed by transglutaminase 2 (TGM2) expression, which enhanced inflammatory cytokine secretion. We further show interferon-γ release and cell surface expression of engulfment (‘eat-me’) signals (such as calreticulin). Finally, combining CI-994 treatment with an anti-CD47 mAb targeting the CD47-SIRPα phagocytosis checkpoint enhanced in vitro phagocytosis and survival in tumor-bearing mice.Conclusion Together, these findings suggest a dynamic relationship between MYC amplification and innate immune suppression in MYC amplified MB and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses. |
| format | Article |
| id | doaj-art-bea518d410cc4fd58c33516272b055a1 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-bea518d410cc4fd58c33516272b055a12025-01-29T09:30:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-01-0111110.1136/jitc-2022-005871Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammationArndt Borkhardt0Nan Qin1Stephen T Keir2Darell D Bigner3Allison Cole4Matthias Wölfl5Viktoria Marquardt6Johanna Theruvath7David Pauck8Daniel Picard9Lena Blümel10Mara Maue11Jasmin Bartl12Ulvi Ahmadov13Maike Langini14Frauke-Dorothee Meyer15Joselyn Cruz-Cruz16Claus M Graef17Till Milde18Olaf Witt19Anat Erdreich-Epstein20Gabriel Leprivier21Ulf Kahlert22Anja Stefanski23Kai Stühler24Julia Hauer25Thomas Beez26Christiane B Knobbe-Thomsen27Ute Fischer28Jörg Felsberg29Finn K Hansen30Rajeev Vibhakar31Sujatha Venkatraman32Samuel H Cheshier33Guido Reifenberger34Thomas Kurz35Marc Remke36Siddhartha Mitra37Division of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyDivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyDepartment of Neurosurgery, Duke University, Durham, North Carolina, USA2 Duke Cancer Institute, Duke University, Durham, NC, USAPediatrics, University of Colorado Denver, Aurora, Colorado, USAUniversity Children`s Hospital, University Medical Center Würzburg, Würzburg, GermanyInstitute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDepartment of Neurosurgery, Institute for StemCell Biology and Regenerative Medicine and Division of Pediatric Neurosurgery, Lucile Packard Children’s Hospital, Stanford University, Stanford, California, USADivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, Germany1Heinrich Heine University, Dusseldorf, NRW, GermanyDivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyDivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyDivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyDivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyDivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyDivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyPediatrics, University of Colorado Denver, Aurora, Colorado, USADepartment of Neurosurgery, Institute for StemCell Biology and Regenerative Medicine and Division of Pediatric Neurosurgery, Lucile Packard Children’s Hospital, Stanford University, Stanford, California, USAHopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, GermanyHopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, GermanyDivision of Hematology-Oncology and Blood and Marrow Transplantation, Department of Pediatrics and the Department of Pathology, Children’s Hospital Los Angeles, and the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USAInstitute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf; and DKTK, partner site Essen/Düsseldorf, Germany, Düsseldorf, GermanyDepartment of Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, GermanyMolecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine University, Düsseldorf, Germany, Düsseldorf, GermanyMolecular Proteomics Laboratory, Biomedical Research Centre (BMFZ), Heinrich-Heine University, Düsseldorf, Germany, Düsseldorf, GermanyDepartment of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany; and DKTK, partner site Essen/Düsseldorf, Germany, Düsseldorf, GermanyDepartment of Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, GermanyInstitute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf; and DKTK, partner site Essen/Düsseldorf, Germany, Düsseldorf, GermanyUniversity Duesseldorf, Duesseldorf, GermanyInstitute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf; and DKTK, partner site Essen/Düsseldorf, Germany, Düsseldorf, GermanyInstitute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyPediatrics, University of Colorado Denver, Aurora, Colorado, USAPediatrics, University of Colorado Denver, Aurora, Colorado, USADepartment of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USADivision of Pediatric Neuro-Oncogenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Düsseldorf, GermanyInstitute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany1Heinrich Heine University, Dusseldorf, NRW, GermanyPediatrics, University of Colorado Denver, Aurora, Colorado, USABackground While major advances have been made in improving the quality of life and survival of children with most forms of medulloblastoma (MB), those with MYC-driven tumors (Grp3-MB) still suffer significant morbidity and mortality. There is an urgent need to explore multimodal therapeutic regimens which are effective and safe for children. Large-scale studies have revealed abnormal cancer epigenomes caused by mutations and structural alterations of chromatin modifiers, aberrant DNA methylation, and histone modification signatures. Therefore, targeting epigenetic modifiers for cancer treatment has gained increasing interest, and inhibitors for various epigenetic modulators have been intensively studied in clinical trials. Here, we report a cross-entity, epigenetic drug screen to evaluate therapeutic vulnerabilities in MYC amplified MB, which sensitizes them to macrophage-mediated phagocytosis by targeting the CD47-signal regulatory protein α (SIRPα) innate checkpoint pathway.Methods We performed a primary screen including 78 epigenetic inhibitors and a secondary screen including 20 histone deacetylase inhibitors (HDACi) to compare response profiles in atypical teratoid/rhabdoid tumor (AT/RT, n=11), MB (n=14), and glioblastoma (n=14). This unbiased approach revealed the preferential activity of HDACi in MYC-driven MB. Importantly, the class I selective HDACi, CI-994, showed significant cell viability reduction mediated by induction of apoptosis in MYC-driven MB, with little-to-no activity in non-MYC-driven MB, AT/RT, and glioblastoma in vitro. We tested the combinatorial effect of targeting class I HDACs and the CD47-SIRPa phagocytosis checkpoint pathway using in vitro phagocytosis assays and in vivo orthotopic xenograft models.Results CI-994 displayed antitumoral effects at the primary site and the metastatic compartment in two orthotopic mouse models of MYC-driven MB. Furthermore, RNA sequencing revealed nuclear factor-kB (NF-κB) pathway induction as a response to CI-994 treatment, followed by transglutaminase 2 (TGM2) expression, which enhanced inflammatory cytokine secretion. We further show interferon-γ release and cell surface expression of engulfment (‘eat-me’) signals (such as calreticulin). Finally, combining CI-994 treatment with an anti-CD47 mAb targeting the CD47-SIRPα phagocytosis checkpoint enhanced in vitro phagocytosis and survival in tumor-bearing mice.Conclusion Together, these findings suggest a dynamic relationship between MYC amplification and innate immune suppression in MYC amplified MB and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses.https://jitc.bmj.com/content/11/1/e005871.full |
| spellingShingle | Arndt Borkhardt Nan Qin Stephen T Keir Darell D Bigner Allison Cole Matthias Wölfl Viktoria Marquardt Johanna Theruvath David Pauck Daniel Picard Lena Blümel Mara Maue Jasmin Bartl Ulvi Ahmadov Maike Langini Frauke-Dorothee Meyer Joselyn Cruz-Cruz Claus M Graef Till Milde Olaf Witt Anat Erdreich-Epstein Gabriel Leprivier Ulf Kahlert Anja Stefanski Kai Stühler Julia Hauer Thomas Beez Christiane B Knobbe-Thomsen Ute Fischer Jörg Felsberg Finn K Hansen Rajeev Vibhakar Sujatha Venkatraman Samuel H Cheshier Guido Reifenberger Thomas Kurz Marc Remke Siddhartha Mitra Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation Journal for ImmunoTherapy of Cancer |
| title | Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation |
| title_full | Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation |
| title_fullStr | Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation |
| title_full_unstemmed | Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation |
| title_short | Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation |
| title_sort | tacedinaline ci 994 a class i hdac inhibitor targets intrinsic tumor growth and leptomeningeal dissemination in myc driven medulloblastoma while making them susceptible to anti cd47 induced macrophage phagocytosis via nf kb tgm2 driven tumor inflammation |
| url | https://jitc.bmj.com/content/11/1/e005871.full |
| work_keys_str_mv | AT arndtborkhardt tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT nanqin tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT stephentkeir tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT darelldbigner tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT allisoncole tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT matthiaswolfl tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT viktoriamarquardt tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT johannatheruvath tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT davidpauck tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT danielpicard tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT lenablumel tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT maramaue tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT jasminbartl tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT ulviahmadov tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT maikelangini tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT fraukedorotheemeyer tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT joselyncruzcruz tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT clausmgraef tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT tillmilde tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT olafwitt tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT anaterdreichepstein tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT gabrielleprivier tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT ulfkahlert tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT anjastefanski tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT kaistuhler tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT juliahauer tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT thomasbeez tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT christianebknobbethomsen tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT utefischer tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT jorgfelsberg tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT finnkhansen tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT rajeevvibhakar tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT sujathavenkatraman tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT samuelhcheshier tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT guidoreifenberger tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT thomaskurz tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT marcremke tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation AT siddharthamitra tacedinalineci994aclassihdacinhibitortargetsintrinsictumorgrowthandleptomeningealdisseminationinmycdrivenmedulloblastomawhilemakingthemsusceptibletoanticd47inducedmacrophagephagocytosisvianfkbtgm2driventumorinflammation |