Bone marrow endothelial cells of patients with multiple myeloma: antigen presenting functions and T cell regulation

Immunity against cancer is hampered by local mechanisms promoting tumor evasion from T cell surveillance or tumor-specific T cell tolerance in the tumor microenvironment. We have analyzed the antigen presenting capacities of endothelial cells from bone marrow of patients with multiple myeloma (MM), an inexorably lethal plasma cell malignancy1. We have found that bone marrow endothelial cells basally express both class I and class II MHC molecules as well as the costimulatory molecules CD80 and CD86. The expression level of these molecules is slightly lower than that of professional antigen presenting cells, such as dendritic cells, from the same patients. Bone marrow endothelial cells also express the components of the MHC class I antigen processing machinery which include the constitutive proteasome subunits delta (beta1), MB1 (beta5) and zeta (beta2); the interferon-gamma (INF-gamma)-inducible proteasome (immunoproteasome) subunits LMP2 (beta1i), LMP7 (beta5i) and LMP10 (beta2i); the peptide transporters TAP1 and TAP2 and the endoplasmic reticulum chaperones calnexin, calreticulin, ERp57 and tapasin. When bone marrow endothelial cells are cultured, CD80 and CD86 expression decreases, class II MHC molecule largely disappears and class I MHC molecule does not significantly change2. Both class II MHC and costimulatory molecule expression are restored by bone marrow endothelial cell exposure to IFN-gamma and IL-6. Cultured bone marrow endothelial cells can activate purified allogeneic and autologous CD4 and CD8 T cells.