The role of tumor-associated macrophages on serum soluble IL-2R levels in B-cell lymphomas

Interkeukin-2 receptor (IL-2R) is comprised of three different subunits (α, β, and γ chain) and is expressed on B cells and NK cells besides T cells. CD25 is also known as the IL-2Rα chain on cell membranes, while soluble IL-2R (sIL-2R) is generated by the proteolytic cleavage of the IL-2Rα chain. Levels of sIL-2R in sera are monitored as a marker of disease activity in patients with lymphoma. However, elevated serum sIL-2R levels are also found in inflammatory diseases, such as infectious diseases. Levels of sIL-2R in sera are thought to reflect tumor burden in adult T-cell leukemia/lymphoma due to the expression of CD25 on tumor cells. Conversely, sIL-2R is thought to be mainly derived from activated T cells infiltrating tumor tissues in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) because lymphoma cells except for a subtype of DLBCL are mainly negative for CD25. Matrix metalloproteinase-9, a protease capable of cleaving the membrane bound IL-2Rα chain, is mainly produced by tissue-associated macrophages. Increased macrophages in tumor tissues are reported to be associated with poor prognosis, especially in Hodgkin's lymphoma. We found increased macrophages in DLBCL and FL compared with reactive lymphoid hyperplasia as well as a positive correlation between the levels of sIL-2R in sera and the number of macrophages in tumor tissues in FL and extranodal DLBCL.