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Moreover, CD107a was expressed by several clones following activation, as it was shown for antiviral CD4+ effectors and tumor-infiltrating lymphocytes.31, 46 Altogether, these data suggest that Surv 97-111-specific CD4+ T cells can exert helper function and direct cytotoxic activity, which are both advantageous for immunotherapy approaches. On the other hand, antigen-specific T regulatory CD4+ cells have been described Epacadostat in vivo by several groups. These findings are a cause for concern in case such cells would expand upon vaccination using antigenic formats like HLA class II epitopes or protein.47�C50 We occasionally observed weak IL-10 production by the Survivin 97-111-induced CD4+ T cells in a minority of patients (3/14 tested before and after vaccination). In two patients tested, TNF-�� and IL-10 were produced by the same cells, but IL-10+CD4+ were rare and constituted the minority of cells producing cytokines upon survivin peptide-stimulation (<2.5% of TNF-��+ cells). However, we cannot exclude the possibility that a subpopulation of Surv 97-111 responding cells may have suppressive properties and this is a topic of further investigation. Finally, we also determined peptide-specific antibody levels in patient sera samples because these have been reported to correlate with a better clinical outcome.33 With 12 patients for whom we could directly compare the magnitudes of T cell and Ab inductions against the applied Surv 97-111 peptide, we observed a tendency for the stimulation of strong antisurvivin T cell responses in association with the absence of antipeptide Ab, but no significant correlation could be established. This aspect will be investigated further and reported after completion of the study together with the detailed T cell and Ab immunomonitoring for all HLA-A2- and HLA-class II-restricted peptides contained in the immunization cocktail, as well as with the clinical course of the patients. Strikingly, we observed induced or increased Surv 97-111-specific CD4+ T cell responses with variable frequencies in the majority <a href="">JQ1 of the patients for which PBMC were tested before and after vaccination. This was the case for at least 10 of the 16 patients; for the remaining 6, 1.V test was not available, but 3 of them show no survivin specific cells at early vaccination timepoints (2.V or 4.V). One individual was found to have detectable anti-Surv 97-111 T cells before vaccination, albeit to a very low frequency (<50 spots in 250,000 cells, not shown). This suggests that the Surv 97-111 epitope can lead to spontaneous T cell activation, at least in some patients with prostate cancer. The multipeptide vaccination was safe and toxicity limited to grade I/II (see interim report, Ref.27). However, it has to be noted that 4 patients reacted with an immediate anaphylactic reaction after several immunizations.</p>