Expression of co-inhibitory molecules B7-H4 and B7-H1 in Epstein-Barr virus positive diffuse large B-cell lymphoma and their roles in tumor invasion

Abstract

To investigate the relationship between immunoregulatory molecules B7-H4 and B7-H1 in Epstein-Barr positive diffuse large B-cell lymphoma (EBV+DLBCL). Immunohistochemistry was used to detect the expression of B7-H4 and B7-H1 in tumor tissues of 13 patients with EBV+DLBCL. The expression levels of B7-H4 and B7-H1 in four diffuse large B-cell lymphoma cell lines (SU-DHL-4, SU-DHL-10, SU-DHL-6, Pfeiffer) were analyzed by flow cytometry. Transwell invasion assays were conducted to observe the invasive ability of cell lines. B7-H4 and B7-H1 were expressed in 84.62% and 100% tumor specimens of EBV+DLBCL. The overexpression of B7-H4 and B7-H1 was found in 46.15% and 23.08% tumor samples of EBV+DLBCL. There was a medium negative correlation between the expression levels of B7-H4 and B7-H1 (r = -0.667, P = 0.013, spearman rank correlation). The expression levels of B7-H1 in four diffuse large B-cell lymphoma cell lines were positively correlated with their invasive ability, whereas the expression levels of B7-H4 were not. Here, we provide evidence for the negative relationship between B7-H4 and B7-H1 in EBV+DLBCL. The expression of B7-H1 in EBV+DLBCL appears to be the dominant factor which affects tumor aggressiveness. When B7-H1 expression weakens, the molecule B7-H4 may become the dominant factor of prognosis in patients with EBV+DLBCL.