Immunosuppressive Microenvironment in Neuroblastoma

Vito Pistoia,Fabio Morandi,Lizzia Raffaghello,Annalisa Pezzolo,Ignazia Prigione,Giovanna Bianchi

doi:10.3389/fonc.2013.00167

Abstract

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.

Highlights

Neuroblastoma (NB) is a pediatric malignancy originating from the neural crest that presents with metastatic disease at diagnosis in approximately a half of patients
We investigated expression of NKG2D ligands in primary NB cells and found that most samples expressed constitutively the transcripts of MICA and MICB, 50% of them tested positive for ULBP2 mRNA, whereas ULBP1 or 3 mRNA were never detected (Raffaghello et al, 2004)
Several immune escape mechanism operated by human NB cells have been reviewed including (i) downregulation of HLA class I related antigen processing machinery (APM) components, that leads to defective antigen presentation and escape from NB-specific CTL recognition, (ii) expression and/or secretion of several immunosuppressive molecules, that inactivate immune effector cells, and (iii) recruitment of immunosuppressive cells, that contribute to the generation of a tumor microenvironment (TM) which impairs anti-tumor immune responses

Summary

Immunosuppressive microenvironment in neuroblastoma

Vito Pistoia*, Fabio Morandi , Giovanna Bianchi , Annalisa Pezzolo, Ignazia Prigione and Lizzia Raffaghello. 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.

INTRODUCTION

Findings

CONCLUSION