Abstract
Immune dysfunction is known to contribute to lymphomagenesis in the context of immunosuppressive therapy and infection with HIV. The current study was undertaken to test whether low grade but progressive forms of lymphoma, mantle cell lymphoma (MCL) and follicular lymphoma (FL), might be associated with systemic immunologic dysfunction as evaluated by flow cytometry. Because of recent studies suggesting a tumor initiating function for infiltrating macrophages in AIDS lymphoma (
Zenger et al, Cancer Research 62:5536–42,2002
), we investigated the immunophenotype of both monocytes and T cells in blood from patients with recurrent MCL and FL. Heparinized blood was taken from 13 individuals with MCL and 6 with FL, both sets of patients previously treated with an average of 4 cycles of combination chemotherapy +/− Rituxan. No patient had received any therapy during the 3 months prior to the current study. Cell surface antigens CD14, CD16, HLA-DR, CD4, CD8, and CD38 were studied in the two diseases and results were compared to age matched controls. Blood from MCL patients showed an immunophenotypic pattern, similar to blood phenotypes described for patients infected with HIV. The %CD4 population was significantly lower than normal controls (p<0.05). The %CD8 T-cell population was elevated when compared to normal (p<0.001) as was the median level of CD38 expression on CD8 T-cells (p<0.01). The CD4/CD8 ratio was inverted (<0.85). Significant elevation of monocyte activation markers was observed in MCL blood when compared to normal controls. Mean fluorescence of HLA-DR on CD14+ cells was elevated (p<0.0001) as was the %CD14+ cells co-expressing CD16 (p<0.0003). By comparison, FL blood showed evidence for both CD4 and CD8 T cell activation with normal CD4/CD8 ratios, however there was no evidence for CD14 cell activation as observed in MCL blood. Taken together, these data suggest that MCL, as a lymphoma subset, shows significant evidence for systemic immune dysfunction and as an acknowledged T cell independent process, shows evidence for macrophage activation, shown recently to potentially play a role in AIDS lymphomagenesis. Further studies on MCL will be required to determine what “factors” might contribute to the persistently abnormal immunophenotype including investigating this class of lymphoma for viral like factors.Author notes
Corresponding author
2005, The American Society of Hematology
2005
