Association of serum B7-H1 level and lymphopenia in diffuse large B-cell non-Hodgkin lymphoma.

Abstract

8080 Background: Activation of the adaptive immune response plays an important role in tumor immune surveillance. Not surprisingly then, lymphopenia has emerged as an adverse prognostic factor in non-Hodgkin lymphoma (NHL). The factors which may contribute to the development of lymphopenia in NHL are incompletely understood. B7-H1, a member of the B7 family of costimulatory/coinhibitory ligands, inhibits T-cell proliferation and promotes the induction of cell death in tumor-specific T cells. We recently described its expression on malignant cells, tumor-infiltrating dendritic cells, and circulating CD14+HLA-DRlo myeloid-derived suppressor cells in NHL (Blood. 2009;114(10): 2149- 58.). Therefore, we have hypothesized that B7-H1 may contribute to the development of lymphopenia in NHL. Methods: Serum samples were collected from normal donors (n=25) and patients with cutaneous T-cell NHL (CTCL, n=24), peripheral T-cell NHL (PTCL, n=29) and diffuse large B-cell lymphoma (DLBCL, n=31) and levels of soluble B7-H1 (sB7-H1) determined by ELISA. Results: Soluble B7-H1 was detected in serum of both normal donors (mean 0.29 ng/mL; 0.09-0.50 95% CI) and CTCL patients (mean 0.44 ng/mL; 0.25-0.63 95% CI), but was found to be significantly elevated in both PTCL (mean 0.84 ng/mL, 0.49-1.20 95% CI, p<0.001) and DLBCL (mean 0.62 ng/mL, 0.49-0.75 95% CI, p<0.001), when compared with that observed in normal donors. In order to determinewhether sB7-H1 may be associated with the development of lymphopenia, sB7-H1 levels at diagnosis were correlated with matched absolute lymphocyte counts (ALC) obtained from DLBCL patients (n=31). An inverse correlation was noted between sB7-H1 and the ALC. Forty-two percent of patients with elevated sB7-H1 (defined as greater than the mean sB7-H1) were lymphopenic (ALC <900/uL) at diagnosis, whereas 16% of the remaining patients were lymphopenic at diagnosis (p=0.1). Following therapy with anthracycline-based chemotherapy, a 39% reduction in sB7-H1 was observed (n=29, p<0.00001, paired t-test) and was associated with an 18% increase in the ALC. Conclusions: Collectively, the data presented demonstrates that sB7-H1 may represent a novel biomarker in NHL that's associated with lymphopenia. No significant financial relationships to disclose.