Background: Recurrent glioblastoma (GBM) are highly aggressive tumors allowing 6-8 month survival. Recent data suggested that tetanus/ diphtheria toxoid (Td) preconditioning could increase dendritic cells (DC) motility and efficacy of vaccination in newly diagnosed glioblastoma patients (Mitchell et al, 2015). Methods: Here we evaluated the possible benefits of immunotherapy with mature DC loaded with autologous tumor lysate in 8 patients with recurrent GBM, who received 24 hours before vaccination ipsilateral vaccine site pre-conditioning with tetanus Td. The primary endpoint was overall survival rate at 9 months after second surgery (OS-9). Patients were analysed for the effector response and the generation of CD8+ and CD4+ T effector and central memory and other relevant immunological parameters in peripheral blood before and after immunization Results: After a median follow-up of 9.6 months median OS was 9.3 (6.5-10.6) months and OS-9 62%. Based on OS > 9 months, five patients were defined, as responder and three asnot responder patients. Four responder patients showed CD8+ T cell activation evaluated as IFNG expression (evaluated by flow cytometry). Three of them also showed the generation of CD8+ T central memory. On the contrary, patients with recurrent GBM we had treated previously with DC vaccination in association with chemotherapy (temozolomide) and without preconditioning, failed to show immunological responses. Conclusions: The results suggest that preconditioning of the vaccine site and absence of temozolomide contribute to CD8+ responses to DC immunotherapy.