Publication Date:
2009-11-20
Description:
Abstract 1953 Poster Board I-976 CD80 is a member of the B7/CD28 family of regulatory proteins. B7/CD28 proteins are expressed on the surface of cells of the adaptive and innate immune system (i.e. lymphocytes, monocyte/macrophages, dendritic cells, myeloid-derived suppressor cells). These proteins function to establish a biologically optimal and dynamic balance between immune activation and inhibition or self-tolerance. Interactions between CD80 and its receptors, which include CD28, CTLA4 and PD-L1, contribute to both stimulatory as well as inhibitory or homeostatic regulation. Galiximab, an antibody directed against CD80, is currently under investigation for the treatment of follicular NHL. Initial clinical trials demonstrated that galiximab is well tolerated and suggest that combining galiximab with rituximab may provide clinical benefit. While expression of CD80 by malignant B cells in non-Hodgkin's lymphoma (NHL) has been reported, these studies utilized poorly quantitative immunohistochemical methods. To gain further understanding of the potential role of CD80 as a therapeutic target in NHL, CD80 expression was evaluated by six-color flow cytometric analysis of primary lymphoma cell suspensions generated from diagnostic biopsies of patients presenting with lymphadenopathy. Results obtained to date confirm that CD80 is uniformly expressed by malignant cells in a large majority of cases of follicular lymphoma (N=63), diffuse large B cell lymphoma (N=38), mantle cell lymphoma (n=7), marginal zone lymphoma (n=12) and small lymphocytic lymphoma (n=9). Furthermore, CD80 expression was also observed on tumor-infiltrating, non-malignant T cells. These results confirm the nearly ubiquitous expression of CD80 by malignant B cells in follicular, diffuse and other low grade NHL. Furthermore, these data demonstrate expression of CD80 by non-malignant cells (e.g. T cells) that define the tumor microenvironment. Further work to expand this dataset and to evaluate the expression of CD80 in non-T, non-B cells is ongoing. The expression of CD80 by malignant cells as well as non-malignant cells in NHL provides an opportunity to not only employ therapeutic antibodies to direct anti-tumor effector function such as antibody-dependent cellular cytotoxicity, but to also potentially interfere with interactions involving CD80 that might be involved in establishing an immune suppressive microenvironment supportive of tumor growth. Disclosures: No relevant conflicts of interest to declare.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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