PD-L1 Expression and Tumor Microenvironment Dynamics in Diffuse Large B-Cell Lymphoma: Immunophenotypic Insights.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of B-cell non-Hodgkin lymphoma (NHL) and is characterized by significant biological and clinical heterogeneity. The programmed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1) immune checkpoint pathway plays a crucial role in tumor immune evasion; however, its diagnostic and prognostic relevance in DLBCL remains unclear. We retrospectively analyzed 66 cases of DLBCL diagnosed between 2017 and 2024 at a single institution. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues using antibodies against PD-L1, PD-1, CD4, CD8, and CD68. Clinical data and histopathological features were correlated with marker expression. Statistical analyses were conducted using IBM SPSS 25, with a significance level set at P < 0.05. PD-L1 expression (greater than 1%) in tumor cells was infrequent (6/66 cases), while immune cell PD-L1 positivity was prevalent (39/66 cases). PD-1 positivity was observed in five tumor samples and 40.9% of stromal immune cells. A significant association was found between tumoral PD-L1 expression and histological subtype (P = 0.015), with anaplastic variants showing higher expression levels. Positive PD-1 expression in immune cells was significantly associated with female gender (P = 0.044). High CD68 expression correlated with a lower Ann Arbor stage (P = 0.040) and tumor morphology (P = 0.010). CD4 and CD8 expression levels showed no significant correlations with clinicopathological features. PD-L1 and PD-1 expression patterns in DLBCL highlight their potential relevance for immune evasion and prognosis, particularly in anaplastic variants. The tumor microenvironment, especially macrophage infiltration, plays a complex role in disease progression. Further studies are needed to validate these findings and investigate therapeutic implications.