Oncolytic virus therapy is a promising direction for cancer treatment. Numerous oncolytic virus strains are under development or examined in clinical trials, there are examples of FDA approved virus vaccines. Although evident progress exists, oncolytic viruses still suffer low efficiency and the mechanisms of their action remain poorly understood. Defects in antiviral mechanisms that include type I interferon (IFN) signaling, contribute to sensitivity of malignant cells to oncolytic viruses, however, this sensitivity significantly differs for different malignant cells. In this project, we present a collection of representative proteomics data for eight primary glioblastoma multiforme (GBM) cell cultures and one culture of normal astrocytes with established sensitivity to type I IFNs that comprehensively characterize the GBM cell responses to type I IFNs. Project consists of three parts: (1) label-free proteomics of primary GBM cultures on Orbitrap Fusion Lumos (a separate dataset); (2) label-free proteomics of primary GBM and normal astrocytes on Orbitrap QExactive HF; (3) label-based proteomics of wild type, IFIT3-deficient and PLSCR1-deficient DBTRG-05MG cells (ATCC) on Q-Exactive Plus.