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

Hum Immunol. 2023 Oct;84(10):551-560. doi: 10.1016/j.humimm.2023.07.007. Epub 2023 Jul 21.

Abstract

Initially discovered in chronic viral infection and then extended to tumor, 'T-cell exhaustion' is a broad term describing the response of T cells to chronic antigen stimulation. 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 and TIGIT, 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, TIGIT and TIM-3 were drastically higher in DLBCL. PTEN, WNT2 and DKK3 expression were also appraised. It was revealed that PTEN was lower in DLBCL, without being statistically significant. In contrast with PTEN, DKK3 and WNT2 were shown to be pronouncedly higher in DLBCL relative to the normal control. Prognostically, only TIGIT was found to be associated with overall survival in DLBCL. Collectively, all the data we curetted from the GEPIA and TIMER 2.0 databases explicitly indicate that CD8+ T cell exhaustion took place, which may be linked with lower PTEN in DLBCL. To the best of our knowledge, this is the first bioinformatic report explicitly proposing that CD8+ T cell exhaustion occurs in DLBCL, which may be associated with lower PTEN.

Keywords: CD8+T; Diffuse large B-cell lymphoma (DLBCL); GEPIA; PTEN; T-cell exhaustion.

MeSH terms

  • B7-H1 Antigen*
  • CD8-Positive T-Lymphocytes
  • Hepatitis A Virus Cellular Receptor 2 / genetics
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • PTEN Phosphohydrolase / genetics
  • Programmed Cell Death 1 Receptor / genetics
  • T-Cell Exhaustion

Substances

  • B7-H1 Antigen
  • Hepatitis A Virus Cellular Receptor 2
  • Programmed Cell Death 1 Receptor
  • PTEN protein, human
  • PTEN Phosphohydrolase