PTEN deletion may be associated with CD8+ T-cell exhaustion in diffuse large B-cell lymphoma

Abstract

Abstract 'T-cell exhaustion' is a broad term describing the response of T cells to chronic antigen stimulation, initially in chronic viral infection and then extended to tumors. By definition, whether T-cell exhaustion occurs in diffuse large B-cell lymphoma (DLBCL) remains largely unknown because little has been described. Here, the immune-suppressing checkpoint molecules involved in T-cell exhaustion, including PD-1, PD-L1, TIM-3, IL-10, IL-6 and IL-2, whose expression levels were analyzed in DLBCL, were retrieved from the GEPIA database. Compared with the normal control, CD8A, TNFA, IFNG and GZMA were markedly elevated in DLBCL, indicating that infiltrated CD8+ T cells predominate in DLBCL. Meanwhile, inhibitory immune checkpoints, such as PD-1, PD-L1, TIM-3, IL-10, IL-6 and IL-2, were significantly higher in DLBCL. PTEN, WNT2, and DKK3 expression was also evaluated. It was revealed that PTEN was lower in DLBCL without being statistically significant. Standing in contrast with PTEN, DKK3 and WNT2 were shown to be pronouncedly higher in DLBCL relative to the normal control. Prognostically, the transcriptional levels of PTEN, CD8A and DKK3 were shown to be unassociated with overall survival in DLBCL. Together, all the data we curetted from the GEPIA and TIMER databases explicitly and strongly indicate that CD8+ T-cell exhaustion may occur, which may be linked with PTEN deletion in DLBCL. To the best of our knowledge, this is the first bioinformatic study explicitly proposing that T-cell exhaustion occurs in DLBCL, which is associated with PTEN loss.