CD57high Neuroblastoma Cells Have Aggressive Attributes Ex Situ and an Undifferentiated Phenotype in Patients

Schlitter, Anne-Marie; Dorneburg, Carmen; Barth, Thomas F.E.; Wahl, Joachim; Schulte, Johannes H.; Brüderlein, Silke; Debatin, Klaus‐Michael; Beltinger, Christian

doi:10.1371/journal.pone.0042025

Cited by 15 publications

(19 citation statements)

References 20 publications

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“…Since CD57 has been found on neuroblastoma and Ewing sarcoma cells with aggressive CSC-like features [15,16], we investigated if CD57 was expressed by the GBM-SCs. CD57 was indeed expressed on all patient-derived GBM-SC lines studied, but it was not lost upon their differentiation, which let us conclude that CD57 is not a bona fide CSC marker for GBM [6].…”

Section: Introductionmentioning

confidence: 99%

“…Transfer to primary or naïve T cells was negligible. Intercellular transfer of CD57 from tumor cells to T cells may have to be considered in the interpretation of phenotyping results for TILs from CD57+ tumor entities such as brain tumors [6,24-26] and neuroectodermal tumors (including neuroblastoma, Ewing's sarcoma, and melanoma [15,16,27,28]), at least in case of in situ analyses such as immunohistochemical analyses. Since the CD57 levels on T cells only slowly decreased over several days after separation from CD57+ tumor cells, the intercellular transfer may even contribute to CD57 expression on effector/memory T cells in PBMCs from patients with CD57+ tumors.…”

Section: Introductionmentioning

confidence: 99%

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Rapid and efficient transfer of the T cell aging marker CD57 from glioblastoma stem cells to CAR T cells

Zhu

Niedermann

2015

Oncoscience

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Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) holds great promise for cancer treatment. We recently developed CAR T cells targeting the prototypic cancer stem cell marker AC133 and showed that these CAR T cells killed AC133+ glioblastoma stem cells (GBM-SCs) in vitro and inhibited the growth of brain tumors initiated from GBM-SCs in xenograft mouse models in vivo. Upon coincubation with GBM-SCs, we observed strong upregulation of the T cell aging marker CD57, but other phenotypical or functional changes usually associated with terminal T cell differentiation could not immediately be detected. Here, we provide evidence suggesting that CD57 is rapidly and efficiently transferred from CD57+ GBM-SCs to preactivated T cells and that the transfer is greatly enhanced by specific CAR/ligand interaction. After separation from CD57+ tumor cells, CD57 epitope expression on T cells decreased only slowly over several days. We conclude that CD57 transfer from tumor cells to T cells may occur in patients with CD57+ tumors and that it may have to be considered in the interpretation of phenotyping results for tumor-infiltrating lymphocytes and perhaps also in the characterization of tumor-specific T cells from tumor or lymph node homogenates or peripheral blood mononuclear cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapid and efficient transfer of the T cell aging marker CD57 from glioblastoma stem cells to CAR T cells

Zhu

Niedermann

2015

Oncoscience

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“…11 CD57, first detected by HNK-1 antibody, is a carbohydrate epitope expressed on cells of neural crest origin, including peripheral nerves in the skin. 12,13 Although the CD57 epitope has been shown to be expressed on adhesion molecules of neural crest stem cells, and is associated with migration of these cells and their invasion and colonization of tissues during development, 14 the role of CD57 expression in type II cells of DCNWPR remains elusive.…”

Section: Discussionmentioning

confidence: 99%

“…10 The similarities between type I cells and differentiated Schwann cells seen in neurofibroma have been pointed out from the view of histological morphology, ultrastructure and immunoreactivity for S100 protein, 3 but the characteristics of type II cells remain unclear. 12,13 Although the CD57 epitope has been shown to be expressed on adhesion molecules of neural crest stem cells, and is associated with migration of these cells and their invasion and colonization of tissues during development, 14 the role of CD57 expression in type II cells of DCNWPR remains elusive. 1 On the other hand, they stain positively for S100 protein, CD57 and NSE.…”

Section: (A) (B)mentioning

confidence: 99%

Four Japanese cases of dendritic cell neurofibroma with pseudorosettes

Hattori

Fukumoto

Anan

et al. 2014

The Journal of Dermatology

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Dendritic cell neurofibroma with pseudorosettes (DCNWPR) is a rare peripheral nerve sheath tumor (PNST). To our knowledge, the only reported case of DCNWPR in Japan was documented by our team. We experienced three additional cases of DCNWPR in our institute since 2007, and report the clinical and histological features of DCNWPR of these Japanese cases. All four patients were adult women, with ages ranging 48-77 years (mean, 63.8). All patients presented with small solitary lesions that were clinically diagnosed as fibroma, melanocytic nevus or mixed tumor of the skin. Three cases were located on the back, and one on the cheek. Histopathologically, well-circumscribed nodules were present in the dermis, and composed of small lymphocyte-like cells with dark nuclei (type I cells) and larger cells with pale vesicular nuclei and abundant eosinophilic cytoplasm (type II cells). Small type I cells were grouped concentrically around the larger type II cells, thereby forming pseudorosettes. Immunohistochemical studies using antibodies against CD57 and S100 protein revealed that type II cells contained a copious cytoplasm endowed with a network of slender dendritic extensions. CD57 should be a useful marker for identifying type II cells because it allows these cells to be stained exclusively. We should recognize DCNWPR with its characteristic histological features such as pseudorosettes and presence of dendritic type II cells as a variant of PNST.

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“…Homology modeling has been successfully used in structure-based design of many therapeutics targeting different types of diseases including cancer (Butler et al, 2010; Schlessinger et al, 2011; DeVore and Scott, 2012). However, it is worth mentioning two categories of excellent protein targets in neuroblastoma that are beyond the scope of homology modeling: first, proteins which have known crystal structures such as CD147, which is associated with decreased neuroblastoma differentiation (Garcia et al, 2009; Wright et al, 2014), and CD57, which has also been implicated in aggression of neuroblastoma (Kakuda et al, 2004; Schlitter et al, 2012). Second, those candidate targets which lack any template structure.…”

Section: Targeting Neuroblastomamentioning

confidence: 99%

Targeting Neuroblastoma Cell Surface Proteins: Recommendations for Homology Modeling of hNET, ALK, and TrkB

Haddad

Heger

Adam

2017

Front. Mol. Neurosci.

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Targeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB). When choosing templates, both sequence identity and structure quality are important for homology modeling and pose the first of many challenges in the modeling process. Homology modeling of hNET can be improved using template models of dopamine and serotonin transporters instead of the leucine transporter (LeuT). The extracellular domains of ALK and TrkB are yet to be exploited by homology modeling. There are several idiosyncrasies that require direct attention throughout the process of model construction, evaluation and refinement. Shifts/gaps in the alignment between the template and target, backbone outliers and side-chain rotamer outliers are among the main sources of physical errors in the structures. Low-conserved regions can be refined with loop modeling method. Residue hydrophobicity, accessibility to bound metals or glycosylation can aid in model refinement. We recommend resolving these idiosyncrasies as part of “good modeling practice” to obtain highest quality model. Decreasing physical errors in protein structures plays major role in the development of targeting agents and understanding of chemical interactions at the molecular level.

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CD57high Neuroblastoma Cells Have Aggressive Attributes Ex Situ and an Undifferentiated Phenotype in Patients

Cited by 15 publications

References 20 publications

Rapid and efficient transfer of the T cell aging marker CD57 from glioblastoma stem cells to CAR T cells

Rapid and efficient transfer of the T cell aging marker CD57 from glioblastoma stem cells to CAR T cells

Four Japanese cases of dendritic cell neurofibroma with pseudorosettes

Targeting Neuroblastoma Cell Surface Proteins: Recommendations for Homology Modeling of hNET, ALK, and TrkB

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