BACKGROUND: Spontaneous anti-tumor immune responses have been detected in several tumor types. However, not only in glioblastoma it is unclear if such immune responses influence patient outcome. METHODS: To detect such immune responses, occurence and frequencies of memory T-cells were determined in the peripheral blood of GBM patients applying the IFN gamma ELISPOT assay and using corresponding tumor lysates (n = 106) or a set of immunogenic polypeptides (n = 32). Extent of resection was assessed by either intraoperative or early postoperative MRI. In addition, intratumoral infiltration of different T-cell subpopulations at the time of first diagnosis was analyzed by immunohistochemistry (n = 20) and compared to the occurrence of spontaneous immune responses. RESULTS: Altogether, T-cell responses against autologous tumor lysate were detected in 61/106 patients. Subsequent survival analysis concentrating on IDH1wt glioblastoma revealed a significant difference towards an improved survival for patients with a spontaneous immune response (p = 0.0251). Most interestingly, when stratifying for the extent of surgery those patients, who got a complete tumor resection and showed a spontaneous T cell response, survived significantly longer (p = 0.0002). In contrast, in subtotally resected patients the immune response did not improve survival. In line with these observations, occurrence of memory T cell responses against a set of known GBM-associated antigens (TTR, MAGE A3, S100A9) also trended to a better survival in those GBM patients who responded to all three antigens (p = 0.0663). Finally, increased frequency of intratumoral T cell infiltrates was also associated with the occurrence of spontaneous immune responses and an improved survival (p = 0.0113). CONCLUSIONS: The present analysis for the first time depicts on several levels a significant influence of the patient's immune system on the course of the disease in GBM patients. In this regard the most crucial prerequisite seems to be the MRI-based complete tumor resection. Most likely surgical removal of the immunosuppressive tumor environment allows for the beneficial reactivation of pre-existing immune responses. SECONDARY CATEGORY: Tumor Biology.