The activation of the NF-κB p65/PD-L1 signaling pathway in AIDS-related PCNSL is related to TNF-α and IFN-γ but not to MYD88 and CD79B mutations
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View abstract on PubMed
Summary
This summary is machine-generated.This study reveals that the NF-κB p65/PD-L1 pathway, activated by TNF-α and IFN-γ, plays a key role in AIDS-related primary central nervous system lymphoma (AR-PCNSL) pathogenesis, offering potential new therapeutic targets.
Area Of Science
- Neuro-oncology
- Immunology
- Molecular Biology
Background
- AIDS-related primary central nervous system lymphoma (AR-PCNSL) has higher mortality than immunocompetent PCNSL (IC-PCNSL), necessitating novel therapeutic strategies.
- The NF-κB p65/PD-L1 signaling pathway is a potential target, but its role in AR-PCNSL pathogenesis remains unclear.
Purpose Of The Study
- To investigate the involvement of the NF-κB p65/PD-L1 signaling pathway in AR-PCNSL.
- To compare clinicopathological and molecular features between AR-PCNSL and IC-PCNSL.
Main Methods
- Analysis of 56 PCNSL tissue samples (32 AR-PCNSL, 24 IC-PCNSL) using HE staining, PD-L1 IHC, EBER ISH, bulk RNA-Seq, and Sanger sequencing.
- Assessment of TNF-α and IFN-γ mRNA levels via RT-PCR and p-NF-κB p65, NF-κB p65, and PD-L1 protein levels via Western blotting.
- Correlation of imaging features (DWI, ADC values) with histopathology.
Main Results
- AR-PCNSL tissues showed increased necrosis, higher PD-L1 and EBER positivity, lower ADC values, and more annular enhancement on DWI compared to IC-PCNSL.
- MYD88 L265P and CD79B mutations were significantly less frequent in AR-PCNSL than in IC-PCNSL.
- Elevated TNF-α and IFN-γ mRNA levels were observed in AR-PCNSL, and their in vitro treatment upregulated p-P65 and PD-L1 expression.
Conclusions
- The NF-κB p65/PD-L1 signaling pathway, activated by TNF-α and IFN-γ, is implicated in AR-PCNSL pathogenesis.
- These findings suggest that targeting this pathway could be a promising therapeutic strategy for AR-PCNSL.
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