Immunotherapy of pediatric brain tumor patients should include an immunoprevention strategy: a medical hypothesis paper

Abstract

Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention.

Perspectives on the immunologic microenvironment of astrocytomas

“…Lastly, this study investigated the possible effect of patient age on the immunologic microenvironment of the astrocytomas studied, as hypothesized by Driggers et al18 Zhang et al19 postulated an antigenic difference between pediatric and adult glioma patients upon studying 16 glioblastomas, four low-grade astrocytomas, 10 juvenile pilocytic astrocytomas, and seven ependymomas. These researchers stated that pediatric brain tumors express fewer tumor antigens when compared with adult glioblastomas, and that glioblastomas derived from adults appeared very antigenic.…”

Cancer-testis and melanocyte-differentiation antigen expression in malignant glioma and meningioma

“…4,23,25,28,[45][46][47][48] To date, a comprehensive expression analysis of both CDA and MDA in glioma is lacking. This study demonstrates by use of the RT-PCR technique that malignant gliomas express particular CTA and MDA.…”

Eosinophil Infiltrates in Pilocytic Astrocytomas of Children and Young Adults

“…Although the pathogenesis of cell origin-dependent TATE is unclear, it may be at least partially attributed to different types of tumour-specific antigens present in those CNS tumours. 17,18,28,38 With the presence of this cell origin-dependent TATE and its dissociation from other peripheral blood elements, the infiltration of eosinophils in astrocytomas seems to be actively involved in their pathogenesis other than a passive reactive process. 12,25 The major finding of our study is that eosinophils are commonly present in pediatric PAs but rarely (only one 20-year-old patient) in adult PAs.…”

“…Pediatric patients with PAs survive longer than adult patients, according to the Central Brain Tumour Registry. 17,18 The discrepancy in outcome between two age groups is attributed to both genetic and nongenetic differences. For example, the glioma-associated antigen precursor protein profile displays the different types between pediatric and adult patients.…”

“…17 In addition, children's immune system undergo development that peaks at puberty, which may also help explain why pediatric patients with PAs survive longer. 18 Reports have inversely associated glioma risk with atopic diseases. [19][20][21] Eosinophils are established effector cells in atopic diseases 22,23 and therefore may be partially responsible for the reported inverse association with atopic diseases and the risk of gliomas.…”