Intra-adrenal murine TH-MYCN neuroblastoma tumors grow more aggressive and exhibit a distinct tumor microenvironment relative to their subcutaneous equivalents

Autor: Daphne Reijnen, Michiel Kroesen, Maaike A. van Hout-Kuijer, Martijn H. den Brok, Ingrid S. Zeelenberg, Ingrid C. Brok, Peter M. Hoogerbrugge, Gosse J. Adema
Rok vydání: 2015
Předmět:
Pathology
medicine.medical_specialty
Cancer Research
Myeloid
medicine.medical_treatment
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Population
Immunology
Adrenal Gland Neoplasms
Mice
Transgenic
Biology
N-Myc Proto-Oncogene Protein
Mouse model
Orthotopic
Mice
Neuroblastoma
Subcutaneous Tissue
Cell Line
Tumor
Adrenal Glands
medicine
Tumor Microenvironment
Immunology and Allergy
Animals
education
Cell Proliferation
Oncogene Proteins
Tumor microenvironment
MHC class II
education.field_of_study
Macrophages
Non Research Personnel Central Animal Laboratory are not attached to an institute / theme
Nuclear Proteins
Immunotherapy
Neoplasms
Experimental
medicine.disease
Primary tumor
Mice
Inbred C57BL
medicine.anatomical_structure
NWP personeel van CDL vallen niet onder een instituut / thema
Oncology
Luminescent Measurements
biology.protein
Female
Original Article
Bioluminescence
Zdroj: Cancer Immunology Immunotherapy, 64, 563-72
Cancer Immunology, Immunotherapy
Cancer Immunology Immunotherapy, 64, 5, pp. 563-72
ISSN: 0340-7004
Popis: In around half of the patients with neuroblastoma (NBL), the primary tumor is located in one of the adrenal glands. We have previously reported on a transplantable TH-MYCN model of subcutaneous (SC) growing NBL in C57Bl/6 mice for immunological studies. In this report, we describe an orthotopic TH-MYCN transplantable model where the tumor cells were injected intra-adrenally (IA) by microsurgery. Strikingly, 9464D cells grew out much faster in IA tumors compared to the subcutis. Tumors were infiltrated by equal numbers of lymphocytes and myeloid cells. Within the myeloid cell population, however, tumor-infiltrating macrophages were more abundant in IA tumors compared to SC tumors and expressed lower levels of MHC class II, indicative of a more immunosuppressive phenotype. Using 9464D cells stably expressing firefly luciferase, enhanced IA tumor growth could be confirmed using bioluminescence. Collectively, these data show that the orthotopic IA localization of TH-MYCN cells impacts the NBL tumor microenvironment, resulting in a more stringent NBL model to study novel immunotherapeutic approaches for NBL. Electronic supplementary material The online version of this article (doi:10.1007/s00262-015-1663-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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