Profiling Immune Escape in Hodgkin's and Diffuse large B-Cell Lymphomas Using the Transcriptome and Immunostaining.

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Immune checkpoint blockade therapies targeting PD-1/PD-L1 are effective in Hodgkin's lymphoma (HL) and some diffuse large B-cell lymphoma (DLBCL) cases.
• Biomarkers predicting response to these therapies remain elusive.
• A novel transcriptional immune escape (IE) scoring system was previously developed and validated in DLBCL.

Purpose of the Study:

• To investigate whether Hodgkin's lymphoma (HL) also exhibits distinct stages of immune escape (IE).
• To compare the immune microenvironment of HL and DLBCL using transcriptomic meta-analysis.

Main Methods:

• Comparative meta-analysis of bulk microarrays from approximately 1000 HL and DLBCL samples.
• Transcriptome deconvolution and immunohistochemistry to analyze tumor-infiltrating lymphocytes (TILs) and immune cell populations.
• Assessment of immune checkpoint molecule expression (PD-1, PD-L1, TIM-3, LAG-3).

Main Results:

• HL samples clustered at an advanced stage of immune escape, distinct from DLBCL.
• HL demonstrated significant enrichment of immune escape and T-cell activation genes.
• HL exhibited higher numbers of CD3+ and CD4+ TILs compared to DLBCL.
• HL showed lower levels of CD68+CD163+ macrophages but higher PD-L1 and LAG-3 expression than DLBCL.

Conclusions:

• Hodgkin's lymphoma (HL) displays an advanced immune activation and escape profile.
• This immune landscape in HL is consistent with its responsiveness to PD-1/PD-L1 blockade therapies.
• Understanding these immune characteristics may aid in developing predictive biomarkers for immunotherapy in HL.