Characterization of bone marrow T cells in monoclonal gammopathy of undetermined significance, multiple myeloma, and plasma cell leukemia demonstrates increased infiltration by cytotoxic/Th1 T cells demonstrating a squed TCR‐Vβ repertoire

BACKGROUND The majority of studies published to date regarding the role of the bone marrow (BM) microenvironment in the pathogenesis of monoclonal gammopathies (MG) have focused on the interaction between stroma cells and plasma cells, whereas information concerning the lymphocytes infiltrating the tumor microenvironment is scanty. METHODS The authors measured the distribution, TCR‐Vβ repertoire, immunophenotype, and functional characteristics of different subsets of BM T lymphocytes from 61 nontreated patients with MG (30 patients with MG of undetermined significance [MGUS], 27 patients with multiple myeloma [MM], and 4 patients with plasma cell leukemia [PCL]). RESULTS The authors found a significantly increased rate of BM infiltration by T cells in all patient groups, at the expense of CD4+CD8− and CD4−CD8− T lymphocytes and both CD4+CD28− and CD8+CD28− cytotoxic/effector T cell subsets, and associated with TCR‐Vβ expansions in both CD4+ and CD8+ BM T cells in the majority of patients with MGUS, MM, and PCL. Moreover, the percentage of T cells secreting interferon (IFN)‐γ was found to be increased (P ≤ 0.05) both in CD4+ and CD8+ T cells in MGUS and MM patients, and a higher plasma concentration of IFN‐γ was found in patients with MM. It is interesting to note that a positive correlation was noted between the proportion of CD28− and both the percentage of IFN‐γ–secreting cells and the proportion of expanded TCR‐Vβ lymphocytes within the total BM CD4+ T cells. CONCLUSIONS The results of the current study demonstrated an increased infiltration of BM by T cells associated with frequent TCR‐Vβ expansions and a more prominent cytotoxic/Th1 phenotype in all the patient groups studied. Cancer 2006. © 2006 American Cancer Society. The majority of studies published to date regarding the role of the bone marrow (BM) microenvironment in the pathogenesis of monoclonal gammopathies (MG) have focused on the interactions between stroma cells and plasma cells, whereas information concerning the lymphocytes infiltrating the tumor microenvironment is scanty. In the current study, the authors show an increased filtration of the BM by T‐cells with frequent TCR‐Vβ expansions in MG patients (n = 61), associated with a more prominent cytotoxic/Th1 phenotype, but without major differences among monoclonal gammopathies of undetermined significance, multiple myeloma and plasma cell leukemia.