PD-L1 Status in Refractory Lymphomas

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Targeted immunotherapy via PD-1/PD-L1 suppression has transformed solid tumor treatment.
• Significant improvements are noted in refractory/relapsing classical Hodgkin lymphoma (cHL).
• PD-1/PD-L1 pathway dysregulation is implicated in various lymphomas.

Purpose of the Study:

• To investigate Programmed death-ligand 1 (PD-L1) expression in diverse therapy-resistant lymphomas.
• To evaluate PD-L1 gene copy number variations (CNV) and co-amplifications.
• To compare the efficacy of different antibody clones and detection methods for PD-L1.

Main Methods:

• Immunohistochemistry (IHC) using SP142 and SP263 antibody clones on 78 therapy-resistant lymphoma samples.
• Next-generation sequencing (NGS) for gene CNV analysis.
• Fluorescent in-situ hybridization (FISH) for PD-L1/JAK2/PD-L2 co-amplification.

Main Results:

• PD-L1 positivity (≥5% cancer cells) was observed in 42-46% of cases, with high concordance between antibody clones.
• Strongest PD-L1 expression was found in classical Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphomas.
• Diffuse large B-cell lymphomas (DLBCL) frequently showed PD-L1 positivity; other lymphoma types showed rare or no positivity.
• PD-L1/JAK2/PD-L2 co-amplifications were detected in 3 cases (DLBCL, cHL).
• FISH detected alterations in all 3 amplified cHL cases, while NGS did not.
• A fraction of IHC-positive cases were FISH/NGS positive, indicating other PD-L1 upregulation mechanisms.

Conclusions:

• PD-L1 is frequently expressed in therapy-resistant cHL and DLBCL, indicating potential for PD-1/PD-L1 targeted immunotherapy.
• FISH may be superior to NGS for detecting PD-L1 alterations in cHL.
• Further research is needed to elucidate other PD-L1 upregulation mechanisms, particularly in DLBCL.