Expression of Functional B7-H2 and B7.2 Costimulatory Molecules and Their Prognostic Implications inDe novoAcute Myeloid Leukemia

Abstract

Purpose: The B7 family molecules have been shown to regulate immune responses in both positive and negative fashions.Their roles in the progression of human cancers, however, are not well established. The aim of this study was to examine whether leukemic cells of acute myeloid leukemia express functional B7 family molecules and, if so, whether such expression has any clinical significance. Experimental Design: The expression of four B7 family molecules, B7.1, B7.2, B7-H1, and B7-H2, on leukemic cells from acute myeloid leukemia patients was analyzed by flow cytometry. The function of the expressed molecules was examined by the allogeneic mixed lymphocyte-leukemic cell reaction, and their relationship to the clinical data and survival was analyzed. Results: Although B7.1and B7-H1expressions were rare, the cells from a substantial number of acute myeloid leukemia cases expressed B7.2 and B7-H2 molecules [mean percentages of B7.2-and B7-H2-positive cells were 28.9% (n = 58) and 15.3% (n = 59), respectively]. Patients in whom >25% of leukemic cells expressed B7-H2 had significantly shorter survival, and this B7-H2 positivity had the strongest prognostic value when B7-H2 and other prognostic factors were analyzed together by multivariate analysis (P = 0.0108). Furthermore, B7.2 expression was associated with hyperleukocytosis (P = 0.026). Consistent with this finding, acute myeloid leukemia cells expressing B7.2 and B7-H2 induced allogeneic CD4 + T cells to proliferate and secrete interleukin-4 and interleukin-10 in vitro, effects that were partially blocked by antibodies against B7.2 and B7-H2. Conclusions: Our results indicate the expression of functional B7.2 and B7-H2 molecules, and these molecules may facilitate progression of acute myeloid leukemia.

CD86+ or HLA-G+ can be transferred via trogocytosis from myeloma cells to T cells and are associated with poor prognosis

“…Transwell experiments demonstrated that cell contact was required for suppression of proliferation. 24 Previous studies demonstrated that an increase in CD86 expression on malignant cells is associated with a poor prognosis in a variety of malignancies including acute myeloid leukemia and thyroid carcinoma 34,35 ; however, there has been a lack of consensus on the prognostic significance of CD86 in myeloma. 36,37 In murine studies, Sabzevari et al analyzed CD80 levels on T cells after stimulation with APCs and demonstrated various levels of CD80 expression.…”

New markers for minimal residual disease detection in acute lymphoblastic leukemia

“…Our findings, however, should spur correlative studies to determine the prognostic significance of the differentially expressed genes, and experiments to ascertain whether they play a role in leukemogenesis and could be targeted for therapy. To this end, overexpression of BCL2 in ALL is associated with prolonged survival of leukemic cells 43 and this molecule can be targeted by specific inhibitors 44 ; HSBP1 (heat shock protein 27), CD86 (B7.2), and CD304 (neuropilin-1) overexpression have been associated with drug resistance and disease progression in AML cells [45][46][47] ; expression of CD200 carries an adverse prognosis in patients with multiple myeloma 48 ; and Abs against CD99 and CD123 have been shown to have effective antitumor activity in murine models of Ewing sarcoma 49 and AML, 50 respectively.…”

The Role of Immune Modulatory MicroRNAs in Tumors

“…In this context, Tamura and coworkers identified an association between low expression of B7-H2 and the escape from immune surveillance indicating that B7-H2 has a potential role in tumorigenesis. B7-H2 [90] is a direct target of miRNA-24, which inhibits B7-H3 expression and therefore is involved in cancer immune evasion. B7-H3 is an immune regulatory molecule, which is often overexpressed in different cancers and associated with metastasis and poor prognosis [91,92].…”