Primary CNS lymphoma commonly expresses immune response biomarkers
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Updated: Dec 25, 2025
HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in Human Chronic Lymphocytic Leukemia Cells
Published on: July 20, 2016
Alexander Ou1, Ashley Sumrall2, Surasak Phuphanich3
1The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Background:
Primary central nervous system lymphoma (PCNSL) is rare and there is limited genomic and immunological information available. Incidental clinical and radiographic responses have been reported in PCNSL patients treated with immune checkpoint inhibitors.
Materials And Methods:
To genetically characterize and ascertain if the majority of PCNSL patients may potentially benefit from immune checkpoint inhibitors, we profiled 48 subjects with PCNSL from 2013 to 2018 with (1) next-generation sequencing to detect mutations, gene amplifications, and microsatellite instability (MSI); (2) RNA sequencing to detect gene fusions; and (3) immunohistochemistry to ascertain PD-1 and PD-L1 expression. Tumor mutational burden (TMB) was calculated using somatic nonsynonymous missense mutations.
Results:
High PD-L1 expression (>5% staining) was seen in 18 patients (37.5%), and intermediate expression (1-5% staining) was noted in 14 patients (29.2%). Sixteen patients (33.3%) lacked PD-L1 expression. PD-1 expression (>1 cell/high-power field) was seen in 12/14 tumors (85.7%), uncorrelated with PD-L1 expression. TMB of greater than or equal to 5 mutations per megabase (mt/Mb) occurred in 41/42 tumors, with 19% (n = 8) exhibiting high TMB (≥17 mt/Mb), 71.4% (n = 30) exhibiting intermediate TMB (7-16 mt/Mb), and 9.5% (n = 4) exhibiting low TMB (≤6 mt/Mb). No samples had MSI. Twenty-six genes showed mutations, most frequently in MYD88 (34/42, 81%), CD79B (23/42, 55%), and PIM1 (23/42, 55%). Among 7 cases tested with RNA sequencing, an ETV6-IGH fusion was found. Overall, 18/48 samples expressed high PD-L1 and 38/42 samples expressed intermediate to high TMB.
Conclusions:
Based on TMB biomarker expression, over 90% of PCNSL patients may benefit from the use of immune checkpoint inhibitors.
Insights
This study reveals that over 90% of primary central nervous system lymphoma (PCNSL) patients show high tumor mutational burden (TMB), suggesting broad potential benefit from immune checkpoint inhibitors for this rare cancer.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Primary central nervous system lymphoma (PCNSL) is a rare malignancy with limited genomic and immunological data.
- Previous observations suggest potential efficacy of immune checkpoint inhibitors (ICIs) in PCNSL patients.
Purpose of the Study:
- To genetically characterize PCNSL and determine the potential benefit of ICIs for a majority of patients.
- To profile mutations, gene amplifications, fusions, and PD-1/PD-L1 expression in PCNSL.
Main Methods:
- Next-generation sequencing (NGS) for mutations, amplifications, and microsatellite instability (MSI).
- RNA sequencing for gene fusions.
- Immunohistochemistry for PD-1 and PD-L1 expression; Tumor Mutational Burden (TMB) calculation.
Main Results:
- High PD-L1 expression observed in 37.5% of patients; PD-1 expression in 85.7% of tumors.
- Tumor Mutational Burden (TMB) ≥5 mt/Mb in 90.5% of tumors, with 19% having high TMB (≥17 mt/Mb).
- Frequent mutations in MYD88 (81%), CD79B (55%), and PIM1 (55%); no MSI detected; ETV6-IGH fusion identified in one case.
Conclusions:
- High TMB and PD-L1 expression in a significant proportion of PCNSL patients suggest potential for ICI therapy.
- Over 90% of PCNSL patients may be candidates for immune checkpoint inhibitor treatment based on TMB biomarker.
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