Clonal Cytotoxic T Cells in Myeloma

Abstract

Multiple myeloma (MM) is a malignant disease characterized by accumulation of morphologically recognizable plasma cells producing immunoglobulin (Ig) in the bone marrow. The occurrence of clonal T cells in MM, as defined by the presence of rearrangements in the T-cell receptor (TCR)-beta chains detected on Southern blotting, is associated with an improved prognosis. This review aims to describe the various ways in which we have demonstrated the presence of such T cell clones, and to describe the phenotype of these cells. Finally, the specificities of these clinically important CD8+ T cell populations will be discussed in the context of immunotherapy.

Clonal expansions of cytotoxic T cells exist in the blood of patients with Waldenström macroglobulinemia but exhibit anergic properties and are eliminated by nucleoside analogue therapy

“…[6][7][8][9][10][11][12][13][14][15] We previously reported that 48% of 120 patients with multiple myeloma have peripheral blood T-cell expansions that show the phenotype of CD3 ϩ CD8 ϩ T-cell receptor V␤-positive (TCRV␤ ϩ ) CD57 ϩ , and we confirmed the clonal nature of these expanded T cells by determining TCRV␤ CDR3 size distribution and direct sequencing. 10,11,16 Although the specificity of these T-cell clones has not yet been determined, several patient cohorts have shown that they persist for long periods and are associated with a good prognosis, suggesting that they may arise after chronic stimulation by a tumor-associated antigen. 5,9,11 Thus, these cells are likely to be tumor-specific cytotoxic lymphocytes with tumor-induced dysfunction.…”

“…16 As similar clonal expansions in patients with multiple myeloma [6][7][8][9][10][11][12][13][14][15] and CML 3 have prognostic significance, it is likely that these cells have an immunoregulatory function toward the tumor cells, although their specificity has yet to be confirmed. The presence of expanded cytotoxic lymphocytes in CML patients after dasatinib therapy was associated with excellent responses.…”

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.…”

Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines, angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome

“…4,8,10 Bone marrow angiogenesis has also been shown to be a prognostic factor in multiple myeloma and pre-clinical work suggests that individual cytokines are important in the biology of myeloma, including effects on angiogenesis.…”