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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1274-1279
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
B7-2-positive myeloma: incidence, clinical characteristics,
prognostic significance, and implications for tumor immunotherapy
Belinda Pope,
Ross
D. Brown,
John Gibson,
Edna Yuen, and
Doug Joshua
From the Institute of Haematology, Royal Prince
Alfred Hospital, Sydney, Australia.
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-regulating the expression of the B7 molecules on malignant
B cells has been shown 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 clinical significance of high CD86
expression on plasma cells at diagnosis and studied the ability of
trimeric human CD40 ligand (huCD40LT) to up-regulate the expression of
the B7 family on malignant plasma cells. CD86 expression 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;  2 = 4.6;
P = .03) and a higher tumor load (patients with more than 50% bone marrow plasma cells, 47% versus 6%;
2 = 7.2; P = .005). CD86 expression was
highest on immature and primitive plasma cells (CD38++,
CD45+) of both patients and controls and was associated
with a CD40+, CD20+, CD19 ,
CD138+ phenotype. The shortened survival was associated
with high CD86 only on mature (CD38++, CD45)
plasma cells (2 = 7.6; P = .006). There
was no significant correlation between high CD86 and other known
prognostic markers, including serum  2-microglobulin,
serum thymidine kinase, and labeling index. The addition of huCD40LT to
short-term cultures up-regulated both CD80 and CD86 expression on B
cells (CD19+) and CD80 on plasma cells
(CD38++), but did not up-regulate CD86 expression on plasma
cells. Thus, B7-2-positive myeloma consists of a subgroup of
patients with a relatively poor prognosis, and CD40LT may be useful in
immunotherapy protocols because it up-regulates CD80 expression on
malignant plasma cells without inducing B7-2-positive myeloma.
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