Frequent expression of PD-L1 in BLS-type diffuse large B-cell lymphoma: implications for aggressiveness and immunotherapy

Ching Fen Yang, Yu Ting Yu, Shu Hsien Wang, Ya Ping Chen, Tsai Yun Chen, Chih Yi Hsu, L. Jeffrey Medeiros, Kung Chao Chang

Research output: Contribution to journalArticlepeer-review

Abstract

BLS-type diffuse large B-cell lymphoma (DLBCL) denotes an uncommon, aggressive variant of DLBCL presenting initially in bone marrow, liver and spleen without lymphadenopathy or mass lesion. Patients with BLS-type DLBCL present frequently with haemophagocytic syndrome which often leads to early patient demise. Programmed death ligand 1 (PD-L1) plays a negative regulatory role on effector T cells and is an important target of immunotherapy. Assessment of PD-L1 expression in BLS-type DLBCL may carry therapeutic implications and provide mechanistic insights. Standard immunohistochemical analysis for PD-L1 was performed in seven cohorts for this study: (1) DLBCL-not otherwise specified (NOS) (n=201); (2) Epstein–Barr virus (EBV)-positive DLBCL (n=26); (3) thymic (primary mediastinal) DLBCL (n=12); (4) intravascular LBCL (n=3); (5) high-grade B-cell lymphoma, NOS (n=12); (6) BLS-type DLBCL (n=37); and (7) systemic DLBCL involving bone marrow (n=28). We found that PD-L1 was positive in 12.9% of DLBCL-NOS cases, 46.2% of EBV-positive DLBCL, 91.7% of thymic LBCL, none of intravascular LBCL, 8.3% of high-grade B-cell lymphoma-NOS, and 56.8% of BLS-type DLBCL. By comparison, only 14.3% of bone marrow cases involved by systemic DLBCL were positive for PD-L1 (p<0.001). Interestingly, BLS-type DLBCL more frequently showed activated B-cell phenotype (86.5% vs 65.2%, p=0.010), a high Ki-67 proliferative index (97.1% vs 63.3%, p<0.001), MYC overexpression (90.9% vs 56.2%, p=0.023), presence of haemophagocytic syndrome (86.5% vs 4.0%, p<0.001), and poorer overall survival (p<0.001) than DLBCL-NOS. These data suggest that the poor prognosis of BLS-type DLBCL may be explained by both extrinsic tumour microenvironment factors and intrinsic genetic factors of tumour cells, such as PD-L1-associated inactivation of anti-tumour immunity for the former, and MYC pathway activation-related aggressiveness for the latter.

Original languageEnglish
Pages (from-to)367-373
Number of pages7
JournalPathology
Volume56
Issue number3
DOIs
Publication statusPublished - 2024 Apr

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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