PD1/PD-L1 Expressions in Plasmablastic Lymphoma with Clinicopathological Correlation

Abstract

The activation of the programmed cell death one (PD1)/PD1 ligand (PD-L1) immune checkpoint pathway is a mechanism of immune evasion characterized by the upregulation of PD-L1 expression by tumor cells and by the tumor microenvironment. This activation leads to the inhibition of PD1-positive T cells and to a decrease in the anti-tumor immune response. Plasmablastic lymphoma (PBL) is an aggressive type of large B-cell lymphoma with limited studies on the frequency of PD1 and PD-L1 expressions and their clinical impact. As PBL is associated with immune suppression in immunocompromised individuals, we hypothesize that the PD1/PD-L1 axis may be relevant in this type of lymphoma. Our study demonstrates a subset of PBL cases with a higher PD-L1 expression by tumor cells [nPD-L1^high, in 4 of 21 (19%) cases] and by tumor microenvironment [macrophages/stromal cells, sPD-L1^high, in 9 of 21 (43%) cases]. While nPD-L1 expression showed no significant correlation with PD1 expression on tumor-infiltrating lymphocytes, or other clinicopathological parameters, it positively correlated with sPD-L1 expression. Moreover, patients with nPD-L1^high had a tendency towards a shorter overall survival (median 9.3 vs. 25.5 months in nPD-L1^low patients). In conclusion, our study provides a rationale to identify, by immunohistochemistry, a subset of nPD-L1^high patients who may benefit from clinical trials of PD1/PD-L1 checkpoint blockade. Further studies on large cohorts are needed to investigate prognostic and predictive biomarkers for the PD1/PD-L1 pathway in PBL patients.

Keywords: EBV; PD-L1; PD1; immune checkpoint; plasmablastic lymphoma.