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Macrophage infiltra...
Macrophage infiltration promotes regrowth in MYCN-amplified neuroblastoma after chemotherapy
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- Valind, Anders (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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- Verhoeven, Bronte Manouk (author)
- Karolinska Institutet,Karolinska Institute
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- Enoksson, Jens (author)
- Skåne University Hospital
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- Karlsson, Jenny (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Christensson, Gustav (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Avdelningen för translationell cancerforskning,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Molekylär evolution,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Division of Translational Cancer Research,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Molecular Evolution
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- Mañas, Adriana (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Aaltonen, Kristina (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Jansson, Caroline (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Bexell, Daniel (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Baryawno, Ninib (author)
- Karolinska Institutet,Karolinska Institute
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- Gisselsson, David (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Northwestern University,Skåne University Hospital: Pediatrics
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- Hagerling, Catharina (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: OncoImmunology. - 2162-4011 .- 2162-402X. ; 12:1
- Related links:
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
Close
- Despite aggressive treatment, the 5-year event-free survival rate for children with high-risk neuroblastoma is <50%. While most high-risk neuroblastoma patients initially respond to treatment, often with complete clinical remission, many eventually relapse with therapy-resistant tumors. Novel therapeutic alternatives that prevent the recurrence of therapy-resistant tumors are urgently needed. To understand the adaptation of neuroblastoma under therapy, we analyzed the transcriptomic landscape in 46 clinical tumor samples collected before (PRE) or after (POST) treatment from 22 neuroblastoma patients. RNA sequencing revealed that many of the top-upregulated biological processes in POST MYCN amplified (MNA +) tumors compared to PRE MNA + tumors were immune-related, and there was a significant increase in numerous genes associated with macrophages. The infiltration of macrophages was corroborated by immunohistochemistry and spatial digital protein profiling. Moreover, POST MNA + tumor cells were more immunogenic compared to PRE MNA + tumor cells. To find support for the macrophage-induced outgrowth of certain subpopulations of immunogenic tumor cells following treatment, we examined the genetic landscape in multiple clinical PRE and POST tumor samples from nine neuroblastoma patients revealing a significant correlation between an increased amount of copy number aberrations (CNA) and macrophage infiltration in POST MNA + tumor samples. Using an in vivo neuroblastoma patient-derived xenograft (PDX) chemotherapy model, we further show that inhibition of macrophage recruitment with anti-CSF1R treatment prevents the regrowth of MNA + tumors following chemotherapy. Taken together, our work supports a therapeutic strategy for fighting the relapse of MNA + neuroblastoma by targeting the immune microenvironment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Child
- Animals
- Humans
- N-Myc Proto-Oncogene Protein
- Neoplasm Recurrence, Local
- Neuroblastoma
- Disease Models, Animal
- Macrophages
- Tumor Microenvironment
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Valind, Anders
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Verhoeven, Bront ...
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Enoksson, Jens
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Karlsson, Jenny
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Christensson, Gu ...
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Mañas, Adriana
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Aaltonen, Kristi ...
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Jansson, Carolin ...
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Bexell, Daniel
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Baryawno, Ninib
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Gisselsson, Davi ...
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Hagerling, Catha ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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OncoImmunology
- By the university
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Lund University
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Karolinska Institutet