Immune Escape Mechanisms and Future Prospects for Immunotherapy in Neuroblastoma.

Thitinee Vanichapol,Somchai Chutipongtanate,Suradej Hongeng,Usanarat Anurathapan

doi:10.1155/2018/1812535

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.

Highlights

Neuroblastoma (NB) is the most common extracranial solid tumor of early childhood, accounting for about 6% of all childhood cancers, with an incidence of 1/70,000 in children younger than 15 years [1]
A similar effect was reported from chimeric antigen receptor (CAR) T cell targeted fibroblast activation protein (FAP); a treatment with the FAP-CAR T cells resulted in ∼80% depletion of FAP+ cells, which was associated with a significant inhibition of tumor growth (35–50%) in mesothelioma and lung cancer mouse models [84]
A paradigm shift in cancer treatment has been achieved through the development of CAR T cells and identification of

Summary

Introduction

Neuroblastoma (NB) is the most common extracranial solid tumor of early childhood, accounting for about 6% of all childhood cancers, with an incidence of 1/70,000 in children younger than 15 years [1]. Genetic engineering of T lymphocytes to express anti-GD2 chimeric antigen receptor (CAR) has been developed and tested in clinical trials This approach represents the novel therapeutic measures in the fight against high-risk NB. Under continuous selection pressure exerted by lymphocytes and cytokines, resistant tumor variants enter the “escape phase” in which they begin to grow progressively without the immunological constraints, establish an immunosuppressive TME, and give rise to clinically overt tumors [12]. These tumor variants are resistant to conventional therapies and are the main cause of mortality in cancer patients.

Mechanisms of Immune Evasion

Overcoming the Immunosuppressive Tumor Microenvironment and Future Prospects

Findings

Conclusion