B7-2-positive myeloma: incidence, clinical characteristics, prognostic significance, and implications for tumor immunotherapy

Deficiencies in B7:CD28 costimulation are considered to be one of the major causes of the failure to generate a tumor-specific immune response. Up-reg ulating the expression of the B7 molecules on malignant B cells has been sh own to stimulate cytotoxic T cells. Plasma cells from patients with myeloma express a tumor-specific idiotype but lack CD80 (B7-1) and have a variable expression of CD86 (B7-2), This study has identified the incidence and cli nical significance of high CD86 expression on plasma cells at diagnosis and studied the ability of trimeric human CD40 ligand (huCD40LT) to up-regulat e the expression of the B7 family on malignant plasma cells. CD86 expressio n on plasma cells was increased in 54% of the patients studied at diagnosis (n = 35) and was associated with a significantly shorter survival (median, 28 versus 57 months; chi(2) = 4.6; P =.03) and a higher tumor load (patient s with more than 50% bone marrow plasma cells, 47% versus 6%; chi(2) = 7.2; P =.005), CD86 expression was highest on immature and primitive plasma cel ls (CD38(++), CD45(+)) of both patients and controls and was associated wit h a CD40(+), CD20(+), CD19(-), CD138(+) phenotype. The shortened survival w as associated with high CD86 only on mature (CD38(++), CD45(-)) plasma cell s (chi(2) = 7.6; P =.006), There was no significant correlation between hig h CD86 and other known prognostic markers, including serum beta(2)-microglo bulin, serum thymidine kinase, and labeling index. The addition of huCD40LT to short-term cultures upregulated both CD80 and CD86 expression on B cell s (CD19(+)) and CD80 on plasma cells (CD38(++)), but did not upregulate CD8 6 expression on plasma cells. Thus, B7-2-positive myeloma consists of a sub group of patients with a relatively poor prognosis, and CD40LT may be usefu l in immunotherapy protocols because it up-regulates CD80 expression on mal ignant plasma cells without inducing B7-2-positive myeloma, (Blood, 2000;96 :1274-1279) (C) 2000 by The American Society of Hematology.