Immunogenicity of diffuse intrinsic pontine glioma (DIPG)

Abstract

Abstract Background Little information exists about the potential immunogenicity and immunotargets for DIPG. Most of the pediatric neurotumors are mainly unexplored immunologically. We studied twenty repository samples of DIPG tumors. We selected two relevant immune markers to demonstrate immune infiltration such as CD8 and Tbet and eight biologically and clinically relevant proteins found in aggressive neoplasias including DIPG. According with this preliminary data DIPG is immunogenic and six of eight relevant proteins were overexpressed. This data will open the possibility to treat this lethal tumor with active antigen-specific immunotherapy either alone and in combination. Methods N=20 repository DIPG pediatric tumors were analyzed by immunohistochemistry (IHC). Moreover we analyzed by granzyme B and IFN-gamma ELISPOT the naturally occurring immune response against predicted Th1 and CD8 epitopes from the eight proteins and we performed univariate and multivariate analysis using SAS/SAT and prism. Results six of eight bad prognosis proteins were overexpressed as following RCAS1 (80%), Fascin-1 (90%), EGFR (55%), VCP (85%), Ape-1 (95%) and Sox2 (70 %). We found 35% of expression of CD8 cells and 40% of Tbet, which is an interesting finding in terms of immune infiltration in DIPG. CD8 antigen specific by Granzyme ELISPOT against Ape-1, RCAS1 and Fascin-1 were significant as well (P=0.0001), (p=0.005) and (9=0.0001), respectively. Discussion DIPG is immunogenic according with our preliminary data and we will expand the number of samples in order to validate a large repository and move to the clinic. We predicted immunogenic peptides for each protein using repository PMBC’s and most of them were recognized by autologous PBMCS’s.