Immune Escape Mechanisms and Future Prospects for Immunotherapy in Neuroblastoma.

Immune Escape Mechanisms and Future Prospects for Immunotherapy in Neuroblastoma. Biomed Res Int. 2018;2018:1812535 Authors: Vanichapol T, Chutipongtanate S, Anurathapan U, Hongeng S Abstract Neuroblastoma (NB) is the most common extracranial solid tumor in childhood with 5-year survival rate of 40% in high-risk patients despite intensive therapies. Recently, adoptive cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, represents a revolutionary treatment for hematological malignancies. However, there are challenges for this therapeutic strategy with solid tumors, as a result of the immunosuppressive nature of the tumor microenvironment (TME). Cancer cells have evolved multiple mechanisms to escape immune recognition or to modulate immune cell function. Several subtypes of immune cells that infiltrate tumors can foster tumor development, harbor immunosuppressive activity, and decrease an efficacy of adoptive cell therapies. Therefore, an understanding of the dual role of the immune system under the influences of the TME has been crucial for the development of effective therapeutic strategies against solid cancers. This review aims to depict key immune players and cellular pathways involved in the dynamic interplay between the TME and the immune system and also to address challenges and prospective development of adoptive T cell transfer for neuroblastoma. PMID: 29682521 [PubMed - in process]
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research

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ierkens Neuroblastoma (NBL) is the most common extracranial solid tumor in childhood. Despite intense treatment, children with this high-risk disease have a poor prognosis. Immunotherapy showed a significant improvement in event-free survival in high-risk NBL patients receiving chimeric anti-GD2 in combination with cytokines and isotretinoin after myeloablative consolidation therapy. However, response to immunotherapy varies widely, and often therapy is stopped due to severe toxicities. Objective markers that help to predict which patients will respond or develop toxicity to a certain treatment are lacking. Immunothera...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
This article presents a case report and comprehensive discussion of the state of the science on metastatic familial (congenital) neuroblastoma. PMID: 31712398 [PubMed - in process]
Source: Neonatal Network - Category: Perinatology & Neonatology Authors: Tags: Neonatal Netw Source Type: research
AbstractPurpose of ReviewWe aim to review the most recent findings in the use of NK cells in childhood cancers.Recent FindingsNatural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less likelihood of cytokine s...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
In this study, we investigated the impact of the human ALK-F1174L mutation in vivo on sympathetic neuroblast differentiation using Sox10-Cre;LSL-ALK-F1174L mice. The aim was to improve our understanding of the implication of ALK deregulated signaling in the initial steps of NB genesis. Results ALK-F1174L Causes Embryonic Lethality When Expressed in NCCs Prior to SA Lineage Commitment To assess the impact of the human ALK-F1174L activating mutation on the development and differentiation of the SNS, Sox10-Cre;LSL-ALK-F1174L embryos were generated. This model allowed to restrict the expression of the ALK-F1174L variant to ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsOur preliminary data demonstrate that NB patients at risk of developing secondary leukemia can be identified by molecular profiling of BM aspirates obtained during routine disease surveillance for NB. These findings present an opportunity for the development of early detection studies for patients with pediatric malignancies undergoing intensive therapy and importantly inform studies into mechanisms of leukemic transformation and specific gene-treatment effects.DisclosuresCheung: Ymabs: Patents &Royalties.
Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis II Source Type: research
(Seattle Children's) Seattle Children's has opened a chimeric antigen receptor (CAR) T-cell immunotherapy trial for children and young adults with relapsed or refractory non-central nervous system EGFR-expressing solid tumors. In the phase 1 trial, STRIvE-01, cancer-fighting CAR T cells will target the EGFR protein expressed in many childhood sarcoma, kidney and neuroblastoma tumors.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Immunotherapeutic strategies are showing promise for pediatric cancers such as leukemia and neuroblastoma. What is the latest research?Chinese Clinical Oncology
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Hematology-Oncology Journal Article Source Type: news
Authors: Veneziani I, Brandetti E, Ognibene M, Pezzolo A, Pistoia V, Cifaldi L Abstract Neuroblastoma (NB), the most common extracranial solid tumor of childhood, causes death in almost 15% of children affected by cancer. Treatment of neuroblastoma is based on the combination of chemotherapy with other therapeutic interventions such as surgery, radiotherapy, use of differentiating agents, and immunotherapy. In particular, adoptive NK cell transfer is a new immune-therapeutic approach whose efficacy may be boosted by several anticancer agents able to induce the expression of ligands for NK cell-activating receptors,...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
AbstractNeuroblastoma (NBL) is the most common extra-cranial solid tumor in childhood. High-risk NBL is considered challenging and has one of the least favourable outcomes amongst pediatric cancers. Primary tumor can arise anywhere along the sympathetic chain. Advanced disease at presentation is common. Diagnosis is established by tumor biopsy and elevated urinary catecholamines. Staging is performed using bone marrow and mIBG scan (FDG-PET/bone scan if mIBG unavailable or non-avid). Age, stage, histopathological grading,MYCN amplification and 11q aberration are important prognostic factors utilized in risk stratification....
Source: Indian Journal of Pediatrics - Category: Pediatrics Source Type: research
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