Several immune escape patterns in non-Hodgkin's lymphomas

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Follicular lymphomas (FL) and diffuse large B cell lymphomas (DLBCL) require immune escape mechanisms for development.
• The specific immune evasion pathways utilized by these lymphomas are not well understood.

Purpose of the Study:

• To investigate and characterize the immune escape strategies employed by FL and DLBCL.
• To compare the expression of key immune checkpoint genes and proteins in FL, DLBCL, and normal B cells.

Main Methods:

• Transcriptome data mining of FL and DLBCL biopsies.
• Definition and analysis of an Immune Escape Gene Set (IEGS).
• Immunohistochemistry (IHC) on tissue microarrays of patient biopsies to confirm protein expression.

Main Results:

• The IEGS, including PD-1, PD-L1, PD-L2, and LAG3, was significantly upregulated in lymphoma samples compared to normal B cells.
• FL samples showed more immune infiltrates and higher rates of PD-1+ lymphocytes.
• DLBCL tumor cells exhibited higher proportions of PD-1+, PD-L1+, PD-L2+, and LAG3+ cells, indicating distinct immune escape strategies.

Conclusions:

• FL and DLBCL utilize distinct immune escape pathways.
• The findings highlight the role of PD-1, PD-L1, PD-L2, and LAG3 in lymphoma immune evasion.
• Activated B cell subtype DLBCL showed higher PD-L1 and PD-L2 expression than the germinal center subtype.