Expression of Galectin-1 by EBV-Positive Lymphoproliferative Disorders
Benjamin J Chen, Jing Ouyang, Papiya Sinha, Margaret A Shipp, Christopher DM Fletcher, Scott J Rodig. Brigham and Women's Hospital & Harvard Medical School, Boston, MA; Dana-Farber Cancer Institute, Boston, MA
Background: Galectin-1 (Gal1) is an immunomodulatory carbohydrate-binding protein upregulated in EBV+ B cells and promotes immune evasion by inducing the apoptosis of EBV-specific CD8+ T cells. We recently showed that Gal1 is expressed by the majority of EBV+ posttransplant lymphoproliferative disorders (PTLDs) and described a novel, neutralizing Gal1 monoclonal antibody that inhibits Gal1-mediated T cell apoptosis, thereby providing a novel therapeutic strategy for the treatment of PTLD (Blood, 2011. 117:4315-22). In this study, we sought to expand the categories of lesions that may benefit from such targeted immunotherapy by examining additional EBV and immunodeficiency-related lymphoproliferative disorders (LPDs) for the expression of Gal1.
Design: Whole tissue sections from 46 tumors were evaluated: 7 EBV+ diffuse large B-cell lymphomas (DLBCL) of the elderly/immunodeficiency-related, 8 plasmablastic lymphomas (PBL), 8 extranodal NK/T-cell lymphomas (ENKTCL), 3 primary effusion lymphomas (PEL), 4 lymphomatoid granulamotosis (LYG), 7 angioimmunoblastic T-cell lymphomas (AITL), 1 hydroa vacciniforme-like lymphoma, 1 EBV+ Burkitt lymphoma (BL), and 7 EBV-negative PTLDs. Immunohistochemistry was performed using a mouse anti-Gal1 monoclonal antibody. Staining intensity (0-3+) and the percentage of positive tumor cells (0-100%) was scored. Staining of 2-3+ in greater than 20% of tumor cells was considered positive.
Results: The majority of EBV+ DLBCLs (5/7), PBLs (6/8), ENKTCLs (6/8), and PELs (3/3) were positive for Gal1 expression. The case of hydroa vacciniforme-like lymphoma was also positive. In contrast, EBV+ BL, EBV+ B cells within LYG and AITL, and all EBV-negative PTLDs were negative for the protein.
Conclusions: We find that a variety of EBV+ tumors, including EBV+ DLBCLs, PBLs, ENKTCLs, and PELs express levels of Gal1 comparable to that observed for EBV+ PTLDs. These results suggest that EBV-mediated Gal1 expression is a general mechanism of immune evasion among LPDs and expands the spectrum of tumors that may benefit from Gal1-directed targeted therapy.
Monday, March 19, 2012 1:00 PM
Poster Session II # 232, Monday Afternoon