Abstract
PURPOSE: Soluble cytotoxic T-lymphocyte antigen 4 (sCTLA-4), one of the isoforms of CTLA-4, was discovered to be critical in downregulating the negative signal of CTLA-4 in T-cell responses. Contrary to the classical immunosuppressive effect of CTLA-4, its immunoregulatory function might be complicated. However, the clinical significance of sCTLA-4 to immune regulation and the variation in cancer therapy have not been elucidated. We postulated that the level of sCTLA-4 might affect the outcome of cancer prognosis. PATIENTS AND METHODS: Serum concentrations of sCTLA-4 before and after therapy in 141 locally advanced and advanced cancer patients were measured and survival analyses was performed. Hazard ratio and 95% confidence interval for overall survival (OS) were calculated. Cutoffs were determined by median across the sCTLA-4 level of entire patients. RESULTS: High expression of sCTLA-4 after therapy indicated significant longer OS and progression-free survival (PFS) (all P<0.01). Among all subgroups, sCTLA-4 levels after therapies were found to be significantly higher than that of 1 day before, which was also negatively correlated with tumor node metastasis stage and lymph node metastasis (all P<0.05). Multivariate analysis revealed that sCTLA-4 level was a strong independent prognostic factor for OS and PFS (all P<0.05). CONCLUSION: Our data demonstrated the favorable prognostic significance of sCTLA-4 and may lead to the development of new immunotherapy options for cancer patients.