Survivin as a Therapeutic Target for Neuroendocrine Neoplasms

Introduction: Although neuroendocrine neoplasms (NENs) have a good prognosis, distant metastasis remains a crucial prognostic factor. Survivin, a tumor-associated antigen, is overexpressed in several solid tumors, indicating poor prognosis. We aimed to evaluate the clinical significance and role of survivin as a therapeutic target for NEN. Methods: We assessed the cytotoxicity of Survivin-2B (a splicing variant of survivin) 80-88 specific CTL clone with HLA-A24 restriction against NEN cell lines using intracellular staining for interferon-γ and assessed the frequency of Survivin-2B 80-88 CTL precursors in nine HLA-A24-positive patients with NEN using tetramer staining and compared it before and after resection. Finally, we evaluated the association between survivin expression and prognosis in 74 patients with pancreatic NEN using immunohistochemistry. Results: Survivin-2B 80-88 CTL clone showed high cytotoxicity against QGP-1 (HLA-A24 positive) cocultured with the Survivin-2B 80-88 peptide. Only three patients were positive for tetramer staining; two showed decreased Survivin-2B 80-88 CTL precursor following resection. The nuclear survivin-low group had a significantly better prognosis than the nuclear survivin-high group. Conclusion: Survivin in NEN is antigenic and may induce cellular immunity via the Survivin-2B CTL precursor. Survivin-targeting immunotherapy can be used to treat NEN with highly expressed Survivin-2B.