Background: CD80 is a member of the B7 family of immune coregulatory proteins that mediate both immune activation and suppression. CD80 in particular has recently been shown to play an important role in supporting immune suppression through interactions with B7-H1. CD80 has been identified as a therapeutic target in non-Hodgkin lymphoma (NHL) based on limited immunohistochemical studies of CD80 expression. Clinical studies have shown that the anti-CD80 antibody galiximab is safe and clinically efficacious in follicular NHL. However, the mechanisms through which targeting CD80 inhibits tumor progression remain poorly understood.Methods: To further define the potential of CD80 as a therapeutic target in NHL, CD80 expression was evaluated by multicolor flow cytometric analysis of primary lymphoma cell suspensions generated from 241 diagnostic biopsies of patients with NHL.Results: CD80 was expressed on malignant B cells in essentially all cases of follicular lymphoma (97%; n 5 115), the majority of cases of diffuse large B-cell lymphoma (90%; n 5 69), marginal zone lymphoma (91%; n 5 22), mantle cell lymphoma (75%; n 5 12), and in about half of small lymphocytic lymphoma cases (43%; n 5 23). CD80 was also present on tumor-infiltrating T lymphocytes in nearly all cases. Additionally, CD80 was expressed by non-B, non-T cells in 68 and 44% of cases of follicular and diffuse large B-cell NHL, respectively.Conclusions: CD80 is expressed on both malignant cells and the nonmalignant cells in NHL. Therapeutic targeting of CD80 will therefore modulate the complex intercellular interactions that define the tumor microenvironment in NHL. V C 2011 International Clinical Cytometry Society