Immunity against cancer cells is at the forefront of fight against highly malignant tumors like glioblastomas (GBM). Autoantibodies and their autoantigen cooperators are one of the promising biomarkers linked to the immune responses and have been reported as having an initiative or prognostic role for certain types of paraneoplastic disorders. Nevertheless, immunoreactivity against antigens expressed in GBM are poorly studied. To date, autoantibodies were identified by pursuing targeted approaches. By contrast, in this study, we collected human GBM tissue and sera samples and by applying proteomics analysis, we determined autoantigen candidates for GBM. Subsequent immunohistochemistry and immunoprecipitation experiments revealed that a solute carrier; SLC3A2 is widely overexpressed in GBMs and therefore, immunoreactivity against SLC3A2 is present in high grade GBM, and SLC3A2 expression is altered in GBMs. No antibody interaction was detected in SLC3A2 expressors of low grade gliomas. Furthermore, autoantibody presence was correlated with prolonged survival of GBM patients. Taken together, for the first time, we reported that the SLC3A2 immunoreaction exists in high grade gliomas with a distinct GBM profile. In conclusion, our findings may open up new avenues for our understanding of glioma prognosis in the context of autoimmunity. This may eventually lead to diagnostic and therapeutic inventions that can be utilized for prevention of the disease progression.