E-Cadherin Expression and Blunted Interferon Response in Blastic Plasmacytoid Dendritic Cell Neoplasm

Area of Science:

• Immunology
• Oncology
• Dermatology

Background:

• Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy originating from plasmacytoid dendritic cells (pDCs).
• Understanding the immunophenotype and tumor microenvironment of BPDCN is crucial for diagnosis and therapeutic strategies.

Purpose of the Study:

• To investigate the expression of E-cadherin (EC) on pDCs in BPDCN and compare it to reactive tissues and other cutaneous conditions.
• To assess the immunomodulatory activity of malignant pDCs in BPDCN, including type I interferon (IFN-I) signaling, PD-L1 expression, and T-cell infiltration.

Main Methods:

• Immunohistochemical analysis of E-cadherin (EC) expression on pDCs in BPDCN, reactive lymph nodes, tonsils, bone marrow, leukemia cutis (LC), and cutaneous lupus erythematosus (CLE).
• Assessment of IFN-I signaling effectors (MX1, ISG5, STAT1 phosphorylation) and downstream targets (IFI27, IFIT1, ISG15, RSAD2, SIGLEC1) in BPDCN and CLE.
• Evaluation of PD-L1/CD274 expression and CD8+ T-cell infiltration in BPDCN.

Main Results:

• E-cadherin (EC) was expressed on pDCs in reactive tissues and highly prevalent in BPDCN (94% cutaneous, 100% nodal/spleen), but undetectable in LC and juxta-epidermal pDCs in CLE.
• BPDCN exhibited significantly lower expression of IFN-I-induced proteins and genes compared to CLE.
• A blunted IFN-I response in BPDCN correlated with reduced CD8+ T-cell infiltration and lack of PD-L1 expression on tumor cells.

Conclusions:

• E-cadherin (EC) serves as a novel diagnostic marker for BPDCN.
• Malignant pDCs in BPDCN may utilize EC-driven signaling to suppress IFN-I responses, fostering a poorly immunogenic tumor microenvironment.
• These findings highlight EC's role in BPDCN pathogenesis and suggest potential therapeutic targets related to immune evasion.