Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients.

CD4(+) T cells have been shown to be crucial for the induction and maintenance of cytotoxic T cell responses and to be also capable of mediating direct tumor rejection. Therefore, the anticancer therapeutic efficacy of peptide-based vaccines may be improved by addition of HLA class II epitopes to stimulate T helper cells. Survivin is an apoptosis inhibiting protein frequently overexpressed in tumors. Here we describe the first immunological evaluation of a survivin-derived CD4(+) T cell epitope in a multipeptide immunotherapy trial for prostate carcinoma patients. The survivin peptide is promiscuously presented by several human HLA-DRB1 molecules and, most importantly, is naturally processed by dendritic cells. In vaccinated patients, it was able to induce frequent, robust and multifunctional CD4(+) T cell responses, as monitored by IFN-γ ELISPOT and intracellular cytokine staining. Thus, this HLA-DR restricted epitope is broadly immunogenic and should be valuable for stimulating T helper cells in patients suffering from a wide range of tumors.

Analysis of tumor antigen-specific T cells and antibodies in cancer patients treated with radiofrequency ablation.

Radiofrequency (RF) ablation is a minimally invasive technique routinely applied for the treatment of primary and secondary liver tumors. It induces cell death by thermal coagulative necrosis of tumor tissues, whereas cellular metabolism can still take place in a transition zone surrounding the necrotic area. An increase in heat shock protein expression occurs shortly after treatment, suggesting that the induction of activating signals may stimulate the host immune system. In addition, various effects on immune effectors have also been observed, including stimulation of tumor-directed T lymphocytes. Here, we prospectively assessed the activation of tumor antigen-specific antibodies, as well as antigen-specific CD4(+) and CD8(+) T cells in patients suffering from primary or secondary malignancies and treated by RF ablation with or without concomitant chemotherapy. An increase of antibodies (in 4 patients of 49), CD4(+) T cells or CD8(+) T cells (in 2 patients of 49) could be detected several weeks to months following intervention. These findings suggest that in addition to the local control of tumor growth, RF ablation can provide the appropriate conditions for activating tumor-antigen specific immune responses.