T‐cell expansions in patients with multiple myeloma have a phenotype of cytotoxic T cells

Abstract

Summary. The presence of T-cell clones in peripheral blood has been previously shown to be associated with a survival advantage in patients with multiple myeloma and suggests that the expanded T-cell populations may be involved in an anti-tumour response. We studied the T-cell receptor (TCR) repertoire of 38 patients with myeloma to identify and characterize the expanded T-cell populations by flow cytometry. T-cell expansions were found in 79% of the patients. The expansions occurred randomly among the 21 variable regions of the TCR b chain (Vb) studied, representing 62% of the V-b repertoire, and were stable during an 18-month follow-up. The phenotype of the expanded V-b populations was predominantly CD8 1 , CD57 1 , CD28 2 and perforin 1 , which differed significantly from the other nonexpanded Vb populations. The expression of the apoptosis markers Fas (CD95) and bcl-2 were similar between the expanded and non-expanded Vb populations. In conclusion, expanded T-cell populations were frequent in patients with myeloma, they remained unchanged during follow-up and had phenotypic characteristics of cytotoxic T cells. These data add further support to the concept that the T-cell expansions may have an immunoregulatory role in myeloma.

Human myeloma cells stimulate the receptor activator of nuclear factor-κB ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease

“…Our in vitro model was supported by the in vivo finding of an increased number of activated T lymphocytes in the BM of MM patients. This observation confirms previous studies showing the presence of an activated T-cell subpopulation 34 with a CD8 clonal expansion [35][36][37] in peripheral blood of MM patients. In addition, the stimulatory effect on RANKL production by T cells was confirmed by the finding of RANKL mRNA expression in BM CD3 ϩ T cells purified from MM patients with massive osteolysis (Ͼ 3 osteolytic lesions) in comparison with patients without osteolysis.…”

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

“…Similarly to what has been previously described for symptomatic MM, 12,[23][24][25] effector CD8 + T and NK cells were also found to be increased in LTDC-MM. Recruitment of cytotoxic cells into the tumor microenvironment could reflect a host immune surveillance mechanism to control tumor growth, which would be inefficient in newly-diagnosed symptomatic patients.…”

High Cytotoxic and Specific Migratory Potencies of Senescent CD8+CD57+ Cells in HIV-Infected and Uninfected Individuals

“…The transcriptional signature of the CD8 ϩ CD57 ϩ cells provides hypotheses about mechanisms involved in apoptosis and lack of proliferation as observed by others (23,(55)(56)(57)(58)(59) in different pathologies and tissues. Confirmation and further exploration of these possible mechanisms should help us to propose new molecules to boost survival, proliferation, and antiviral capacity of CD8 ϩ CD57 ϩ cells, especially in HIV infection.…”