title: Intra-adrenal murine TH-MYCN neuroblastoma tumors grow more aggressive and exhibit a distinct tumor microenvironment relative to their subcutaneous equivalents.
abstract: 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.
authors: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences/278 TIL, Radboud University Medical Center, Post Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors: Michiel
authors: M
authors: Kroesen
authors: Ingrid C
authors: IC
authors: Brok
authors: Daphne
authors: D
authors: Reijnen
authors: Maaike A
authors: MA
authors: van Hout-Kuijer
authors: Ingrid S
authors: IS
authors: Zeelenberg
authors: Martijn H
authors: MH
authors: Den Brok
authors: Peter M
authors: PM
authors: Hoogerbrugge
authors: Gosse J
authors: GJ
authors: Adema
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D000311:Adrenal Glands / Q000166:cytology / Q000276:immunology / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D008163:Luminescent Measurements; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000071447:N-Myc Proto-Oncogene Protein; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D040521:Subcutaneous Tissue / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins