Peripheral EBV antigen-specific T cell is dysfunctional in Epstein-Barr virus positive diffuse large B-cell lymphoma

Area of Science:

• Immunology
• Oncology
• Virology

Background:

• EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is linked to poor prognosis, potentially due to Epstein-Barr virus (EBV) suppressing anti-tumor immunity.
• A functional deficiency in EBV antigen-specific T lymphocytes may contribute to this poor outcome.

Purpose of the Study:

• To investigate the mechanisms behind the functional deficiency of peripheral T cells in EBV+ DLBCL patients.
• To examine the phenotypes and function of T cells in EBV+ DLBCL, EBV-negative DLBCL (EBV- DLBCL), and healthy controls.

Main Methods:

• ELISPOT and flow cytometry were used to analyze peripheral T cells.
• Study included 6 EBV+ DLBCL patients, 54 EBV- DLBCL patients, and 12 healthy controls.

Main Results:

• EBV+ DLBCL patients showed significantly reduced IFN-γ secreting T cells upon EBV peptide stimulation compared to EBV- DLBCL patients.
• EBV+ DLBCL exhibited decreased proportions of total lymphocytes, CD8+ T cells, CD4+ central memory T cells, CD8+ naive T cells, and CD8+ effector T cells.
• Elevated PD-1 expression on CD4+ and CD8+ T cells, reduced CD4+TIM-3-CTLA-4- population, and diminished CD8+ T cell IFN-γ expression were observed in EBV+ DLBCL.

Conclusions:

• Functional deficits in EBV antigen-specific T cells in EBV+ DLBCL correlate with altered T cell subset distributions.
• Heightened levels of T cell exhaustion and senescence, along with diminished immune effector molecule expression, characterize EBV+ DLBCL.
• These T cell dysfunctions likely contribute to the poor prognosis associated with EBV+ DLBCL by impairing anti-tumor immunity.