Aberrant expression and reverse signalling of CD70 on malignant B cells

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• CD27 and its ligand CD70 are tumor necrosis factor receptor superfamily members with restricted expression in normal lymphoid tissues.
• Previous studies indicated dysregulated CD27 expression in B-cell leukaemias and lymphomas.

Purpose of the Study:

• To investigate the expression and function of CD70 in various B-cell malignancies.
• To determine if CD70 can act as a receptor in malignant B cells.

Main Methods:

• Immunohistochemistry to assess CD70 expression in patient samples.
• Flow cytometry and cell proliferation assays.
• Monoclonal antibody stimulation to investigate CD70 and CD27 signaling.

Main Results:

• CD70 is expressed in a significant proportion of B-cell chronic lymphocytic leukaemias (B-CLLs), follicle centre lymphomas, large B-cell lymphomas, and mantle cell lymphomas.
• CD70 expression often presents as a capped appearance, co-occurring with CD27.
• A subset of B-CLLs proliferated in response to CD70 stimulation, an effect enhanced by CD40 ligation and inhibited by IL-4.
• This proliferation was mediated by an agonistic CD70 signal, not CD27-mediated negative signaling blockade.

Conclusions:

• CD70 is aberrantly expressed in various B-cell malignancies.
• In a subset of malignant B cells, CD70 can function as a receptor, delivering proliferative signals.
• CD70's potential role as a receptor may contribute to the progression of B-cell malignancies.