gms | German Medical Science

Objective: Despite multimodal treatment, the prognosis of patients with glioblastoma (GBM) WHO grade IV remains dismal. Recently, immunotherapeutic approaches have experienced a revival, but the underlying mechanisms and prerequisites are yet to be discovered. The MHC class I human leucocyte antigens (HLA) -A, -B and -Cw are constitutively expressed cell surface molecules that present antigens to T cells. Knowledge about the distribution of HLA polymorphisms in glioma patients therefore helps (1) to tailor peptide-based immunotherapy and (2) to identify the inherited susceptibility to glioma. However, there are only few case series with mixed histology addressing this question. We therefore sought to elucidate the class I HLA distribution in a large cohort of primary (p)GBM.

Method: 98 Caucasian patients with histologically confirmed pGBM treated at our department between 1990 and 2009 were investigated. Blood samples were collected prior to tumour resection with written informed consent. Genomic DNA was extracted from peripheral blood leucocytes, amplified by PCR and typing of HLA-A, -B and -Cw was performed by the standard Sequence Specific Primer (SSP-PCR) amplification method. Allele frequencies were compared to those of 174 healthy Caucasian controls from Essen, Germany (www.allelefrequencies.net; Ferencik S & Grosse-Wilde H, HLA 1997), employing the Fisher's exact test and the relative risk (RR). A p-value <0.05 was considered statistically significant.

Results: 59 male and 39 female patients with a median age of 59 years (range 20-80 years) were included in the study. Median overall survival was 13 months (range 0-279 months) with 5 patients alive at the time of analysis. HLA-A*02 (48%) and HLA-Cw*07 (48%) were most frequently detected, but with similar frequency in the control population (51% and 59%, resp.). Compared to healthy controls, HLA-A*29 (p=0.049; RR=2.73), HLA-B*18 (p=0.046; R=2.49) and HLA-Cw*16 (p=0.0027; RR=8.09) were significantly over-represented and HLA-B*08 (p=0.0447; RR=0.58) under-represented in pGBM patients.

Conclusions: Analysing a large and histologically well-defined cohort, this study revealed four class I HLA polymorphisms, namly HLA-A*29, HLA-B*18, HLA-Cw*16 and HLA-B*08, to be differentially distributed in Caucasian pGBM patients compared to healthy controls. Whether the first three confer a potential predisposition for pGBM, needs clarification in future studies. In addition, these results contribute to the tailored development of tumour peptide-based vaccines.