Bone Marrow-Infiltrating Human Neuroblastoma Cells Express High Levels of Calprotectin and HLA-G Proteins

Morandi, Fabio; Scaruffi, Paola; Gallo, Fabio; Stigliani, Sara; Moretti, Stefano; Bonassi, Stefano; Gambini, Claudio; Mazzocco, Katia; Fardin, Paolo; Haupt, Riccardo; Arcamone, Giampaolo; Pistoia, Vito; Tonini, Gian Paolo; Corrias, Maria Valeria

doi:10.1371/journal.pone.0029922

Cited by 41 publications

(58 citation statements)

References 49 publications

(58 reference statements)

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“…In a recent study comparing gene expression profiles of primary vs. metastatic NB tumors we have found that the latter tumors upregulated with the highest score expression of calprotectin and HLA-G mRNA (Morandi et al, 2012). It is therefore conceivable that different mechanisms contribute to HLA-G production in human NB, i.e., instruction of other cell types by primary tumor cells and direct production of HLA-G by metastatic NB cells.…”

Section: Neuroblastoma-derived Soluble Factors As Mediators Of Escapementioning

confidence: 97%

Immunosuppressive Microenvironment in Neuroblastoma

et al. 2013

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According to the cancer immunoediting model, the interplay between tumor cells and the host immune system is crucial for the control of tumor growth. NB is a pediatric tumor that presents with metastatic disease at diagnosis in about 50% of the cases, the majority of which have poor prognosis. In this Review article, immune escape pathways adopted by human neuroblastoma (NB) cells are reviewed. These include intrinsic defects of tumor cells such impaired expression of the HLA class I related antigen processing machinery and functional alterations of the tumor microenvironment (TM) induced by NB cell-derived immunosuppressive molecules as MICA and HLA-G. Finally, examples of therapeutic interventions targeting the TM are discussed to emphasize the concept that successful cancer treatment may be achieved using this strategy.

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Section: Neuroblastoma-derived Soluble Factors As Mediators Of Escapementioning

confidence: 97%

Immunosuppressive Microenvironment in Neuroblastoma

et al. 2013

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“…They express or release proteins to inhibit 92–9495–96 , and to kill, T-cells and NK cells 97 . They even recruit tissue macrophages to disable these lymphocytes 98 .…”

Section: Immunology and Immunotherapymentioning

confidence: 99%

Neuroblastoma: developmental biology, cancer genomics and immunotherapy

2013

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Neuroblastoma is a solid tumor that arises from the developing sympathetic nervous system. Over the past decade, our understanding of this disease has advanced tremendously. The future challenge is to apply the knowledge gained toward developing risk-based therapies and ultimately improving outcome. Here we review the key discoveries in the developmental biology, molecular genetics, and immunology of neuroblastoma, as well as new translational tools to bring these promising scientific advances into the clinic.

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“…In this study, Morandi et al . mainly focused on the identification of genes differentially expressed between diagnostic DTCs and primary tumors to identify genes which could serve as prognostic markers for high‐risk neuroblastoma patients …”

Section: Introductionmentioning

confidence: 99%

Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression

Rifatbegovic¹,

Frech²,

Abbasi³

et al. 2017

Intl Journal of Cancer

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Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of metastatic (M) stage patients present with disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and relapse. Although these cells represent a major obstacle in the treatment of neuroblastoma patients, insights into their expression profile remained elusive. The present RNA‐Seq study of stage 4/M primary tumors, enriched BM‐derived diagnostic and relapse DTCs, as well as the corresponding BM‐derived mononuclear cells (MNCs) from 53 patients revealed 322 differentially expressed genes in DTCs as compared to the tumors (q < 0.001, |log2FC|>2). Particularly, the levels of transcripts encoded by mitochondrial DNA were elevated in DTCs, whereas, for example, genes involved in angiogenesis were downregulated. Furthermore, 224 genes were highly expressed in DTCs and only slightly, if at all, in MNCs (q < 8 × 10−75 log2FC > 6). Interestingly, we found the transcriptome of relapse DTCs largely resembling those of diagnostic DTCs with only 113 differentially expressed genes under relaxed cut‐offs (q < 0.01, |log2FC|>0.5). Notably, relapse DTCs showed a positional enrichment of 31 downregulated genes on chromosome 19, including five tumor suppressor genes: SIRT6, BBC3/PUMA, STK11, CADM4 and GLTSCR2. This first RNA‐Seq analysis of neuroblastoma DTCs revealed their unique expression profile in comparison to the tumors and MNCs, and less pronounced differences between diagnostic and relapse DTCs. The latter preferentially affected downregulation of genes encoded by chromosome 19. As these alterations might be associated with treatment failure and disease relapse, further functional studies on DTCs should be considered.

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Bone Marrow-Infiltrating Human Neuroblastoma Cells Express High Levels of Calprotectin and HLA-G Proteins

Cited by 41 publications

References 49 publications

Immunosuppressive Microenvironment in Neuroblastoma

Immunosuppressive Microenvironment in Neuroblastoma

Neuroblastoma: developmental biology, cancer genomics and immunotherapy

Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression

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