High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression...

Area of Science:

• Oncology
• Virology
• Immunology

Background:

• Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas.
• Viral infections, particularly Epstein-Barr virus (EBV), have been implicated in certain PTCL subtypes.
• A comprehensive analysis of the virome across diverse PTCL subtypes was lacking.

Purpose of the Study:

• To conduct a comprehensive virome analysis across PTCL subtypes using existing and new RNA-sequencing data.
• To investigate viral gene expression and its impact on tumor phenotype and the immune microenvironment.
• To explore potential roles of EBV and other oncogenic viruses in PTCL pathogenesis.

Main Methods:

• Utilized whole-transcriptome RNA sequencing (RNA-seq) data from seven PTCL studies and new data.
• Screened for viral associations and analyzed viral gene expression patterns.
• Assessed B- and T-cell receptor diversity and deconvoluted immune cell subpopulations.

Main Results:

• Identified Epstein-Barr virus (EBV) in angioimmunoblastic T-cell lymphoma (AITL), extranodal NK/T-cell lymphoma (ENKTL), and anaplastic large-cell lymphoma (ALCL).
• Detected Kaposi's sarcoma-associated herpesvirus and human T-cell leukemia virus type 1 in isolated PTCL cases.
• Observed EBV lytic gene expression in AITLs, increased B-cell presence, and heightened B-cell receptor diversity, suggesting EBV-driven polyclonal responses.

Conclusions:

• Findings suggest alternative roles for EBV in PTCLs beyond canonical oncogenic mechanisms.
• Results indicate potential involvement of other human tumor viruses in PTCL pathogenesis.
• The study highlights immunological alterations associated with these viral infections in PTCLs.