Clinicopathologic implication of PD-L1 and phosphorylated STAT3 expression in diffuse large B cell lymphoma

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Programmed cell death ligand 1 (PD-L1) shows efficacy in lymphomas.
• Phosphorylated STAT3 (pSTAT3) is implicated in non-GCB DLBCL.
• Investigating PD-L1 and pSTAT3 in EBV-negative DLBCL.

Purpose of the Study:

• To explore associations between PD-L1 expression/gene alteration, pSTAT3, and clinicopathologic features in EBV-negative DLBCL.
• To determine the prognostic significance of PD-L1 and pSTAT3 in DLBCL subtypes.
• To understand the interplay between PD-L1 and pSTAT3 in DLBCL pathogenesis.

Main Methods:

• Analyzed PD-L1 and pSTAT3 expression via immunohistochemistry in 107 DLBCL cases.
• Assessed PD-L1 gene translocation and copy number alterations using FISH.
• Correlated molecular findings with clinicopathologic variables and survival outcomes.

Main Results:

• PD-L1 expression (tumor and immune cells) and pSTAT3 were more frequent in non-GCB DLBCL.
• PD-L1 gene alterations were observed in 10% of cases.
• pSTAT3 independently predicted shorter progression-free survival (PFS) in DLBCL.
• Immune cell PD-L1 (PD-L1i) correlated with shorter PFS in pSTAT3-negative R-CHOP-treated patients.

Conclusions:

• PD-L1 and pSTAT3 expression/alteration are linked and characteristic of non-GCB DLBCL.
• pSTAT3 has independent prognostic value in DLBCL.
• Immune cell PD-L1 (PD-L1i) has clinical significance in a pSTAT3-dependent manner, informing immunotherapeutic strategies and risk stratification.