LOH in the HLA Class I Region at 6p21 Is Associated with Shorter Survival in Newly Diagnosed Adult Glioblastoma

Purpose: Glioblastoma (GBM) shows downregulated expression of human leukocyte antigen (HLA) class I, thereby escaping from cytotoxic T cells and limiting the efficacy of immunotherapy. Loss of heterozygosity (LOH) of HLA class I (6p21) and/or beta-2 microglobulin (B2m) (15q21) regions represents irreversible downregulation. In this study, we examined the prevalence of these LOH events and their relations with overall survival in GBM. Experimental Design: In a cross-sectional analysis on 60 adult patients with GBM, DNA from formalin-fixed, paraffin-embedded specimens were evaluated for 10 microsatellite regions of HLA class I, B2m, HLA class II, HLA class III, and 6q by PCR as well as immunohistochemical evaluation of HLA class I expression and CD8(+) T-cell infiltration. Results: LOH in HLA class I, B2m, HLA class II, HLA class III, and 6q regions was present in 41.4%, 18.2%, 9.4%, 77.8%, and 36.0% of informative cases, respectively. LOH of HLA class I was associated with shorter overall survival (HR = 4.89, P = 0.0078). HLA class I was downregulated in 22% to 43% of cases based on immunohistochemistry. Cases that displayed negative staining were significantly younger. HLA class I expression correlated with intratumoral CD8(+) T-cell infiltration. Conclusion: LOH in the HLA class I region is frequent in adult GBMs. The association of shorter survival with LOH in this region suggests a crucial role for these genes in immunosurveillance. Clin Cancer Res; 19(7); 1816-26. (C)2013 AACR.