T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells

Area of Science:

• Immunology
• Oncology
• Hematology

Background:

• Circulating monocytes and neutrophils are prognostic factors in diffuse large B-cell lymphoma (DLBCL).
• Myeloid-derived suppressor cells (MDSCs) are implicated in various diseases, including DLBCL, but their mechanisms remain unclear.
• MDSCs are a heterogeneous population comprising monocytic (M-MDSC) and granulocytic (G-MDSC) subsets.

Purpose of the Study:

• To investigate the presence and immunosuppressive mechanisms of MDSC subsets in DLBCL.
• To identify potential correlations between MDSC counts and clinical prognostic factors in DLBCL patients.

Main Methods:

• Gene expression profiling to identify a myeloid suppressive signature in DLBCL peripheral blood.
• Flow cytometry to quantify circulating G-MDSC and M-MDSC subsets in 66 DLBCL patients.
• Assessment of T-cell proliferation restoration after monocyte depletion and analysis of immunosuppressive factors.

Main Results:

• Elevated circulating G-MDSC and M-MDSC counts were identified in DLBCL patients.
• M-MDSC numbers correlated with the International Prognostic Index, event-free survival, and regulatory T-cell counts.
• T-cell proliferation was restored upon monocyte depletion, indicating myeloid-dependent suppression.
• Immunosuppression was attributed to interleukin-10, S100A12 release, and increased PD-L1 expression.

Conclusions:

• Expanded MDSC subsets are present in DLBCL.
• Novel mechanisms of immunosuppression involving M-MDSCs, IL-10, S100A12, and PD-L1 contribute to DLBCL pathogenesis.
• MDSCs represent potential therapeutic targets in DLBCL.