TNF-α and IFN-γ modulate the evasion of the immune response in primary mediastinal B-cell lymphoma.

Objectives: Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that shares features with diffuse large B-cell lymphoma (DLBCL), but also with classical Hodgkin lymphoma (cHL). PMBCL often contains aberrations of genes involved in the immune response such as cREL and PD-L1, whose expression is also influenced by cytokines TNF-α and IFN-γ.

Methods: In this study, cell lines Farage, U2940, MedB-1 and Karpas1106p were used as PMBCL models and treated with different concentrations of TNF-α and IFN-γ over 24 and 48 h, followed by the quantification of cREL, CXCL10 and PD-L1 expression. Additionally, the expression of TNF-α, IFN-γ, cREL, CXCL10, CXCR3, PD-L1 and PD-1 genes was compared between PMBCL tissue samples and B-cell and T-cell rich zones of non-tumour tonsils.

Results: Prolonged exposure to TNF-α increased cREL expression, while IFN-γ strongly induced CXCL10 expression. The change in the expression of PD-L1 in response to the treatments differed across various cell lines. There was no statistically significant difference in the expression of the target genes between tumour and non-tumour patient tissue samples.

Conclusions: the obtained results suggest that the immune checkpoints in PMBCL cells are affected by both their genetic profile and tumour microenvironment.