Distinct T-cell clonal expansion in the vicinity of tumor cells in plasmacytoma

BACKGROUND. Although various clinical observations suggested that myeloma cell growth might be modulated by the immune system, evidence supporting the in situ immunogenicity of myeloma cells remains scarce. The authors reasoned that if there is any specific T-cell/tumor cell interaction in myeloma, it is most likely reflected in the T-cell population in the vicinity of the tumor cells. METHODS. The authors used a molecular method to compare the T-cell populations in the vicinity of tumor cells with those in the peripheral blood in patients with plasmacytomas and multiple myeloma. RESULTS. Six patients were studied. When compared with the peripheral blood from the corresponding patients. T cells in the vicinity of tumor cells in five of the six patients showed significant contraction of the T-cell receptor (TCR) Vβ repertoire. In addition to this, the T cells isolated from the sites of the tumor cells from four of these five patients also demonstrated significant increase in the number of TCR Vβ gene families with restricted number of CDR3 size peaks and loss of the normal CDR3 size gaussian distribution pattern. These findings were observed in patients who experienced recurrence after allogeneic stem cell transplantation and also in those who had autologous stem cell transplant. They also were found in previously untreated myeloma patients. In all six patients, distinct TCR Vβ recurring transcripts indicative of a T-cell clonal expansion were found in the vicinity of the tumor cells and either absent or detected at only a low frequency in the peripheral blood. CONCLUSIONS. Our results provide evidence for an in situ local T-cell clonal expansion in the vicinity of tumor cells and support the presence of specific T-cell/tumor cell interaction in myeloma.