The Serine Protease CD26/DPP4 in Non-Transformed and Malignant T Cells

SIMPLE SUMMARY: The transmembrane serine protease CD26/Dipeptidylpeptidase 4 modulates T-cell activation, proliferation, and effector function. Due to their remarkable tumoricidal properties CD26-positive T cells are considered promising candidates for T cell-based immunotherapies while in cutaneous T cell lymphoma CD26/DPP4 expression patterns are established markers for diagnosis and possibly prognosis. With a focus on T cells, we review current knowledge on the regulation of CD26/DPP4 expression and release, its implication in T-cell effector function and the suitability CD26/DPP4 as a diagnostic and/or prognostic factor in T-cell malignancies. ABSTRACT: CD26/Dipeptidylpeptidase 4 is a transmembrane serine protease that cleaves off N-terminal dipeptides. CD26/DPP4 is expressed on several immune cell types including T and NK cells, dendritic cells, and activated B cells. A catalytically active soluble form of CD26/DPP4 can be released from the plasma membrane. Given its wide array of substrates and interaction partners CD26/DPP4 has been implicated in numerous biological processes and effects can be dependent or independent of its enzymatic activity and are exerted by the transmembrane protein and/or the soluble form. CD26/DPP4 has been implicated in the modulation of T-cell activation and proliferation and CD26/DPP4-positive T cells are characterized by remarkable anti-tumor properties rendering them interesting candidates for T cell-based immunotherapies. Moreover, especially in cutaneous T-cell lymphoma CD26/DPP4 expression patterns emerged as an established marker for diagnosis and treatment monitoring. Surprisingly, besides a profound knowledge on substrates, interaction partners, and associated signal transduction pathways, the precise role of CD26/DPP4 for T cell-based immune responses is only partially understood.