“Re-educating” Tumor Associated Macrophages as a Novel Immunotherapy Strategy for Neuroblastoma

Neuroblastoma is the most common extracranial pediatric tumor and often presents with metastatic disease, and patients with high-risk neuroblastoma have survival rates of ~50%. Neuroblastoma tumorigenesis is associated with the infiltration of various types of immune cells, including myeloid derived suppressor cells, tumor associated macrophages (TAMs), and regulatory T cells, which foster tumor growth and harbor immunosuppressive functions. In particular, TAMs predict poor clinical outcomes in neuroblastoma, and among these immune cells, TAMs with an M2 phenotype comprise an immune cell population that promotes tumor metastasis, contributes to immunosuppression, and leads to failure of radiation or checkpoint inhibitor therapy. This review article summarizes the role of macrophages in tumor angiogenesis, metastasis, and immunosuppression in neuroblastoma and discusses the recent advances in “macrophage-targeting strategies” in neuroblastoma with a focus on three aspects: (1) inhibition of macrophage recruitment, (2) targeting macrophage survival, and (3) reprogramming of macrophages into an immunostimulatory phenotype.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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ABSTRACT Background: Neuroblastoma is a pediatric tumor with a mortality rate of 40% in the most aggressive cases. Tumor microenvironment components as immune cells contribute to the tumor progression; thereby, the modulation of immune cells to a pro-inflammatory and antitumoral profile could potentialize the immunotherapy, a suggested approach for high-risk patients. Preview studies showed the antitumoral potential of BJcuL, a C- type lectin isolated from Bothrops jararacussu venom. It was able to induce immunomodulatory responses, promoting the rolling and adhesion of leukocytes and the activation of neutrophils. Methods...
Source: Journal of Venomous Animals and Toxins including Tropical Diseases - Category: Tropical Medicine Source Type: research
Anti-GD2 monoclonal antibody (dinutuximab) has improved survival for high-risk neuroblastoma, but many children recur with resistant disease. We discovered that neuroblastoma cells treated with natural killer (aNK) cells and dinutuximab lead to tumor cell death and subsequent acquisition of neuroblastoma GD2 by aNK cells (GD2+aNK), a phenomenon called trogocytosis. We hypothesized that trogocytosis can be validated in vivo and that GD2+aNK cells would be targeted by aNK cells in the presence of dinutuximab in vitro.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Pediatric surgery Source Type: research
AbstractFaithful tumor mouse models are fundamental research tools to advance the field of immuno-oncology (IO). This is particularly relevant in diseases with low incidence, as in the case of pediatric malignancies, that rely on pre-clinical therapeutic development. However, conventional syngeneic and genetically engineered mouse models fail to recapitulate the tumor heterogeneity and microenvironmental complexity of human pathology that are essential determinants of cancer-directed immunity. Here, we characterize a novel mouse model that supports human natural killer (NK) cell development and engraftment of neuroblastoma...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Aberrant expression of glycosphingolipids (GSLs) is a unique feature of cancer and stromal cells in tumor microenvironments. Although the impact of GSLs on tumor progression remains largely unclear, anticancer immunotherapies directed against GSLs are attracting growing attention. Here, we focus on GD2, a disialoganglioside expressed in tumors of neuroectodermal origin, and Globo H ceramide (GHCer), the most prevalent cancer ‐associated GSL overexpressed in a variety of epithelial cancers. We first summarize recent advances on our understanding of GD2 and GHCer biology and then discuss the clinical development of the fir...
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Review Article Source Type: research
Conditions:   Constitutional Mismatch Repair Deficiency Syndrome;   Hematopoietic and Lymphoid Cell Neoplasm;   Lynch Syndrome;   Recurrent Lymphoma;   Recurrent Malignant Solid Neoplasm;   Recurrent Neuroblastoma;   Recurrent Primary Central Nervous System Neoplasm;   Refractory Lympho ma;   Refractory Malignant Solid Neoplasm;   Refractory Neuroblastoma;   Refractory Primary Central Nervous System Neoplasm;   Xeroderma Pigmentosum Interventions:   Proced...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Contributors : Florida Voli ; Emanuele Valli ; Luigi Lerra ; Kathleen Kimpton ; Federica Saletta ; Federico M Giorgi ; Daniele Mercatelli ; Jourdin R Rouaen ; Sylvie Shen ; Jayne E Murray ; Aria Ahmed-Cox ; Giuseppe Cirillo ; Chelsea Mayoh ; Paul A Beavis ; Michelle Haber ; Joseph A Trapani ; Maria Kavallaris ; Orazio VittorioSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTherapeutic checkpoint antibodies blocking PD1/PD-L1 signaling have radically improved clinical outcomes in cancer. However, the regulation of PD-L1 expression on tumor cells is still poorly understood. Here we show...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Conditions:   Pediatric Solid Tumor;   Germ Cell Tumor;   Retinoblastoma;   Hepatoblastoma;   Wilms Tumor;   Rhabdoid Tumor;   Carcinoma;   Osteosarcoma;   Ewing Sarcoma;   Rhabdomyosarcoma;   Synovial Sarcoma;   Clear Cell Sarcoma;   Malignant Peripheral Nerve Sheath Tumors;   Desm oplastic Small Round Cell Tumor;   Soft Tissue Sarcoma;   Neuroblastoma;   Melanoma Interventions:   Biological: second generation 4-1BBζ B7H3-EGFRt-DH...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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