BACKGROUND: Tumor-infiltrating T cells have a positive influence on the clinical course of B cell non-Hodgkin's lymphoma (NHL). T cells in the peripheral blood of patients with B cell NHL, however, have so far rarely been examined. METHODS: Using flow cytometry we examined lymphocyte subpopulations and numbers of naïve/memory T cell subtypes among peripheral T cells of patients with B cell NHL (N=22), patients with metastasized solid tumors (N=27), and healthy controls (N=20). In addition, we analyzed the intracellular content of effector molecules granzyme B and perforin and expression of the T cell receptor zeta chain. RESULTS: We observed increased percentages of potentially highly cytotoxic CD8+CD56+ T cells in the peripheral blood of patients with NHL. Both, patients with NHL and patients with solid tumors showed a much higher expression of the chemokine receptors CCR4 and CCR5 on their T cells than healthy controls, suggesting a polarization of their T cells following stimulation with antigen and/or cytokines in vivo. Furthermore, patients with B cell NHL and patients with solid tumors had far lower percentages of naïve CD45RA+CCR7+ T cells than healthy controls and, in the case of CD4+ T cells, patients with solid tumors. In contrast, patients with B cell NHL showed markedly increased levels of memory effector CD45RA-CCR7- CD4(+) T cells when compared to healthy controls and patients with metastasized solid tumors. Patients with NHL also showed elevated levels granzyme B within CD8(+) T cells, indicating that the increase in memory effector cells was of functional relevance. CONCLUSIONS: These findings indicate a marked shift in the composition of peripheral T cells of patients with B cell NHL from naïve to memory effector-type cells.
BACKGROUND: Tumor-infiltrating T cells have a positive influence on the clinical course of B cell non-Hodgkin's lymphoma (NHL). T cells in the peripheral blood of patients with B cell NHL, however, have so far rarely been examined. METHODS: Using flow cytometry we examined lymphocyte subpopulations and numbers of naïve/memory T cell subtypes among peripheral T cells of patients with B cell NHL (N=22), patients with metastasized solid tumors (N=27), and healthy controls (N=20). In addition, we analyzed the intracellular content of effector molecules granzyme B and perforin and expression of the T cell receptor zeta chain. RESULTS: We observed increased percentages of potentially highly cytotoxic CD8+CD56+ T cells in the peripheral blood of patients with NHL. Both, patients with NHL and patients with solid tumors showed a much higher expression of the chemokine receptors CCR4 and CCR5 on their T cells than healthy controls, suggesting a polarization of their T cells following stimulation with antigen and/or cytokines in vivo. Furthermore, patients with B cell NHL and patients with solid tumors had far lower percentages of naïve CD45RA+CCR7+ T cells than healthy controls and, in the case of CD4+ T cells, patients with solid tumors. In contrast, patients with B cell NHL showed markedly increased levels of memory effector CD45RA-CCR7- CD4(+) T cells when compared to healthy controls and patients with metastasized solid tumors. Patients with NHL also showed elevated levels granzyme B within CD8(+) T cells, indicating that the increase in memory effector cells was of functional relevance. CONCLUSIONS: These findings indicate a marked shift in the composition of peripheral T cells of patients with B cell NHL from naïve to memory effector-type cells.
Authors: Camilo E Fadul; Jan L Fisher; Jiang Gui; Thomas H Hampton; Anik L Côté; Marc S Ernstoff Journal: Neuro Oncol Date: 2011-02-20 Impact factor: 12.300