Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer.

Abstract

BackgroundTapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8+ cytotoxic T lymphocyte (CTL) infiltration of colorectal cancer (CRC) and overall survival.MethodsA next-generation tissue microarray (ngTMA) of 198 CRC patients with full clinicopathological information was included in this study. TMA slides were immunostained for tapasin, MHC I and CD8. Marker expression was analyzed with immune-cell infiltration, patient survival and TNM-staging.ResultsA reduction of tapasin expression strongly correlated with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95 % CI 1.7–5.0), lymphatic invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3–3.3), distant metastasis (AUC 0.727, OR 2.9, p = 0.004; 95 % CI 1.4–5.9) and an infiltrative tumor border configuration (AUC 0.621, OR 2.2, p = 0.017; 95 % CI 1.2–4.4). Further, tapasin expression was associated with CD8+ CTL infiltration (AUC 0.729, OR 5.4, p < 0.001; 95 % CI 2.6–11), and favorable overall survival (p = 0.004, HR 0.6, 95 % CI 0.42–0.85).ConclusionsConsistent with published functional data showing that tapasin promotes antigen presentation, as well as tumor immune recognition and destruction by CD8+ CTLs, a reduction in tapasin expression is associated with tumor progression in CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0647-1) contains supplementary material, which is available to authorized users.