Cancer Immunotherapy, targets Survivin, and Establishment of Evaluation Methods of Therapeutic Effects

在本研究中，我们建立了可靠的四聚体染色和ELTSPOT检测技术，可以监测survivin-2B肽的特异性免疫反应。结果表明，将survivin - 2b肽与IFA和IFN-a接种可有效诱导肽特异性免疫应答。然而，疫苗接种不能有效地诱导临床反应，在大多数情况下具有细胞减少作用。在许多不能诱导临床反应的病例中，MHC I类表达水平在主要病灶下调。因此，我们认为MHC I类表达水平的下调可能是疫苗接种虽然诱导了肽特异性ms，但仍不能有效诱导临床反应的原因之一。此外，我们还研究了在我院手术病例中MHC I类表达水平与预后的关系。MHC I类表达水平下调的患者生存率低于未下调的患者。因此MHC I类表达水平可能是恶性潜能的新指标。在本研究中，我们得出结论，肽疫苗治疗的最合适适应症可能是MHC I类表达水平未下调的低级别病例。

In this research, we established firm techniques of tetramer staining and ELTSPOT assay, which could monitor the survivin-2B peptide specific immunological responses. We made out that the vaccination using the surviving-2B peptide with IFA and IFN-a could efficiently induce the peptide specific immunological responses. However, the vaccination could not effectively induce the clinical responses, which have cytoreductive effects in most cases. In many cases which could not be induced the clinical responses, the MHC class I expression level was down-regulated in the primary focus. So, we concluded that the down-regulation of MHC class I expression level might be one of the reasons that the vaccination could not efficiently induce the clinical responses in despite of the induction of the peptide specific Ms. In addition, we investigated the relationship between the MHC class I expression level and the prognosis in cases that were operated in our hospitals. The survival rate of the cases that have the down-regulation of the MHC class I expression level was lower in comparison with the cases that do not have the down-regulation. So the MHC class I expression level might be the novel indication of malignant potential. In this research, we concluded that the most suitable indication of the peptide vaccine therapy might be low-grade cases that the MHC class I expression level was not down-regulated.