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-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; chi(2) = 4.6; P =.03) and a higher tumor load (patients 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 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 (chi(2) = 7.6; P =.006). There was no significant correlation between high CD86 and other known prognostic markers, including serum beta(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. (Blood. 2000;96:1274-1279)
Pope
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Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia.
Brown
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Gibson
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Yuen
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Joshua
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology*; D051940:B7-2 Antigen; D005260:Female; D006801:Humans; D007167:Immunotherapy; D015994:Incidence; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D011379:Prognosis
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins