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By affecting immunological presentation, the presence of cytomegalovirus in some glioblastomas may impact progression. In this study, we examined a hypothesized role for natural killer (NK) cells in impacting disease progression in this setting. We characterized 108 glioblastoma patients and 454 healthy controls for HLA-A,-B,-C, NK-cell KIR receptors, and CMV-specific antibodies and correlated these metrics with clinical parameters. Exome sequences from a large validation set of glioblastoma patients and control individuals were examined from in silico databases. We demonstrated that the KIR allele KIR2DS4*00101 was independently prognostic of prolonged survival. KIR2DS4*00101 displayed 100% concordance with cognate HLA-C1 ligands in glioblastoma patients, but not controls. In the context of both HLA-C1/C2 ligands for the KIR2DS4 receptor, patient survival was further extended. Notably, all patients carrying KIR2DS4*00101 alleles were CMV seropositive, but not control individuals, and exhibited increased NK-cell subpopulations, which expressed the cytotoxicity receptors CD16, NKG2D, and CD94/NKG2C. Finally, healthy controls exhibited a reduced risk for developing glioblastoma if they carried two KIR2DS4*00101 alleles, where protection was greatest among Caucasian individuals. Our findings suggest that KIR2DS4*00101 may offer a molecular biomarker to identify intrinsically milder forms of glioblastoma. Cancer Res; 76(18); 5326–36. ©2016 AACR.

Background Identification of families with hereditary nonpolyposis colorectal cancer (HNPCC) allows for surveillance that has been proved to reduce morbidity and mortality from colorectal cancer (CRC). The HNPCC subset can broadly be divided into tumors caused by germline mismatch-repair (MMR) gene mutations, referred to as Lynch syndrome (LS), and those with an undefined genetic background, designated as familial colorectal cancer type X (FCC-X). Recognition of FCC-X tumor is challenging due to the lack of MMR defect and limited information is available about the global gene expression patterns in FCC-X tumors. We aimed at comprehensive pathway mapping of the global gene expression profile in FCC-X tumors with comparison to LS and sporadic CRC as controls. Materials and methods Tumour specimens were obtained from the national Danish HNPCC Register. RNA was extracted from 3-5 10-µm sections using the High Pure RNA Paraffin Kit (Roche, Castle Hill, Australia). The Whole-genome cDNA-mediated annealing selection extension and ligation (DASL) assay (Illumina, San Diego, CA) containing >24,000 probes in >18,000 genes was used for whole genome expression analysis. Expression values were analysed using the GenomeStudio software (Illumina, San Diego, CA) and imported into MeV 4.6.02. Canonical pathways were identified using DAVID Bioinformatics Resources 6.7. Results RNA was obtained from 180 tumors (60 LS, 60 FCC-X, 30 sporadic MSI-CRC and 30 sporadic MSS-CRC. Samples with Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-439. doi:1538-7445.AM2012-LB-439