Abstract
The outcome for patients with localized prostate cancer (LPCa) is markedly variable, with different survival rates. The objective of the present study was to investigate how the levels of blood-related soluble factors and the densities of immune T-cell subsets could impact the prognosis of LPCa. The progression-free survival of 139 patients with LPCa was retrospectively analyzed after standard treatments. Survival was revealed to be associated with the levels of circulating HER-2/neu extracellular domain (HER-ECD), transforming growth factor β (TGFβ) and interleukin-8 (IL-8), as well as with the frequencies of total and prostate-specific antigen (PSA)-peptide-specific CD8(+) T-cell subsets. Based on these analyses, patients with LPCa could be grouped into those having lower levels of HER-ECD, TGFβ and IL-8 [designated as the favorable biosignature (FB)] and increased survival, and those with higher levels [designated as the unfavorable biosignature (UB)] and decreased survival. Patients with the FB exhibited significantly higher densities of total circulating effector memory (EM) CD8(+) T cells and lower densities of the corresponding CD8(+) terminal EM (TEMRA) T cells as compared with the group of patients with localized disease and decreased survival (UB group). Notably, patients bearing the FB had similarly high survival irrespective of their Gleason score. Moreover, patients with the FB had preexisting immunity to PSA, expressed by increased frequencies of PSA((153-161)) peptide-specific EM CD8(+) T cells in the context of decreased numbers of PSA((153-161)) peptide-specific TEMRA CD8(+) T cells. The present data indicated the prognostic potential of circulating HER-ECD, TGFβ and IL-8 levels, and of CD8(+) EM and TEMRA cell frequencies for risk stratification of patients with LPCa.