Neuroblastoma is a tumor of the nervous system in children. It has been noted that children of a younger age (less than 1 year) do much better in terms of survival than older children. Age has been one of the criteria to classify these children to the three groups of low, intermediate or high risk. The treatment and prognosis differ among these groups with only a third of the high risk patient surviving long term.

The human body fights against infection as well as tumors using the immune system. The immune system functions by two different pathways, the innate and the adaptive. The innate system is nonspecific and is the primary defense in infants. As the child grows, the adaptive system develops which produces a specific response and defense. It has been noted in previous studies that components of the innate system are more active in fighting against neuroblastoma.

Studies in Neuroblastoma so far have aimed at fighting the disease directly. I this study, we want to study the ability of the patient’s own immune system to fight the disease The aim of our study is to test the hypothesis that components of the innate system predict low risk neuroblastoma whereas components of the adaptive system predict high risk neuroblastoma. In other words, we try to clarify whether the difference in outcomes between the young and older patients with neuroblastoma in part depends on their relative immune system – innate vs. adaptive. This will be studied by looking at the immune function genes in the tumor tissue of these two groups as well as the products of these genes. For example, cytokines, and interleukins which are proteins that affect and facilitate activity of other cells in the blood of these patients. We also aim to look at the same components in patients whose disease relapse (recurred) and determine signatures of the immune function genes which could have led to relapse. The main objective of this study is to identify biomarkers for low risk and high risk neuroblastoma and predict risk of relapse.

Progress to date:

The study was approved by the VCU Institutional review board and we have been acquiring patient samples in our clinic as well as developed collaboration with the Children’s Oncology Group for acquisition of patient samples. It has been conducted as a pilot study to gather preliminary information and so far we have about 15 samples and the results have been encouraging. We have been able to isolate 2 previously unidentified genes by RT-PCR, which could be playing a role in low risk patients. We have also been able to identify 3 cytokines which could be playing a role in the expression of these genes. The pattern of the immune response genes in the microarray analysis as well in the cellular components of the peripheral blood shows a distinct difference between the low risk and the high risk groups. These results were accepted and presented as a poster at the annual meeting of the American Society of Pediatric Hematology Oncology in Montreal, Canada in April ’10.

Further work:

We would like to expand our study to include a larger number of patient samples, as a larger number of samples studied will increase the statistical significance of the results.

Some of the steps that we propose to study include:

1. Microarray analysis of a larger sample to look for genes of immune functions (approximately 25 samples in each group) to reconfirm our current observations.

2. Immunohistochemistry of the samples to confirm which of the genes we have detected, are being functional in producing proteins.

3. Development of a ‘signature’ which can be used to differentiate the group of patients who will fare well from those who will not.

4. Cell culture studies where we add cytokines to neuroblastoma cell lines in culture plates. This will tell us if we can replicate what happens in the human body in an artificial setting.

5. Development of molecules which can stimulate the innate immune system so as to improve survival in patients who have high risk disease.