What is the Role of Soluble Cytokine Receptors in Adult T-cell Leukemia/ Lymphoma?

Abstract

Soluble cytokine receptors are products of tumor cells infected with viruses such as human T-cell leukemia virus type 1 (HTLV-1). Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive leukemia/lymphoma caused by HTLV-1. High levels of soluble cytokine receptors are detected in the serum of patients with ATLL. Matrix metalloproteinase (MMP)-9 cleaves the interleukin (IL)-2 receptor α chain (IL-2Rα, CD25), which produces soluble IL-2Rα (sIL-2R) and down-regulates the proliferative capability of T cells that encounter cancer cells. Soluble CD30 (sCD30) impairs the interaction of CD30 ligand+ cells with CD30+ cells, whereas CD30 expression integrates survival signals to NK cells. Accordingly, high level of sIL-2R and sCD30 suggest that not only does impaired tumor surveillance lead to the survival of ATLL cells, but also dysfunction of immune surveillance can cause severe infectious complications. Freshly isolated leukemic cells from acute type ATLL patients express little CD30 on the surface, and predominantly produce sCD30. Proliferating ATLL cells are thought to release sCD30, and excess sCD30 probably blocks CD30L on normal activated T cells and myeloid cells, protecting CD30+ ATLL cells from apoptosis. Regarding CD30, two types of MMPs have been reported, ADAM10 and ADAM17, and Tax expression may be associated with ADAM17 activation in HTLV-1-infected cells. Thus, soluble cytokine receptor, sCD30, is both a serum component and a functional protein. Detection of sCD30 level may be useful for detecting and monitoring Tax-expressing tumor cells in vivo.