Abstract A87: Characterization of the involvement of transcriptional repressor IRF2BP2 on T-cell proliferative response
Authors: Barbara L. M. O Vieira, Cristiane S. Secca, Giuliana Mognol, Anjana Rao, João P. B. Viola
Journal: Clinical Cancer Research (2018)

Abstract IRF2BP2 (Interferon Regulatory Factor-2 Binding Protein-2) is a transcriptional repressor involved in the regulation of gene expression in several different biologic contexts. It has been shown that IRF2BP2 expression is induced by the tumor suppressor protein p53 during genotoxic stress in osteosarcoma cell lines, which leads to a prevention of cell death. At least two translocations generating fusion genes involving IRF2BP2 were described distinct types of neoplasia as the IRF2BP2-CDX1 in chondrosarcoma and the IRF2BP2-RARA in acute promyelocytic leukemia. Recently, our group demostrated that IRF2BP2 represses NFAT1 (Nuclear factor of activated T-cells) transcriptional activity in CD4 T lymphocytes. In the present work we investigate the involvement of IRF2BP2 in the biology of CD4 T lymphocytes activation. We showed that ectopic expression of IRF2BP2 repressing CD4 T cell proliferation induced upon activation. We did not observe any differences in cell death of transduced cell cultures overexpressing IRF2BP2; however, we did observe a deleterious role in cell survival in the presence of an apoptotic stimulus by making these cells more prone to die after irradiation. In vivo, transferred IRF2BP2-overexpressing transduced CD4 T cells displayed an impaired expansion capacity compared to controls. Next, we generated a genetic model of conditional transgenic mice that overexpresses IRF2BP2 on T lymphocytes (IRF2BP2fl/flLck-cre+). Analysis by qRT-PCR demonstrated that CD4 T lymphocytes from IRF2BP2fl/flLck-cre+ mice presented an 8- to 10-fold increase of IRF2BP2 mRNA in comparison to wild-type animals (IRF2BP2+/+Lck-cre-). To evaluate the involvement of IRF2BP2 overexpression in T cell homeostasis we characterized the lymphocyte population in the thymus, spleen, and peripheral lymph nodes. In fact, IRF2BP2fl/flLck-cre+ animals showed a decrease in the total T-cell population in lymph nodes and thymus compared with controls. Furthermore, our results showed a reduction on CD3+ cells and a compensatory increase in B220+ compartment in the spleen and lymph nodes. IRF2BP2fl/flLck-cre+ animals also showed fewer counts of CD4+ and CD8+ cells in the thymus, spleen, and lymph nodes. Taken together, our data suggest a role for IRF2BP2 in controlling different parameters of CD4 T-cell function such as proliferation and cell survival, and may act as a regulator of immunologic checkpoint. Financial Support: FAPERJ, CNPq, INCT-Cancer. Citation Format: Barbara L. M. O Vieira, Cristiane S. Secca, Giuliana Mognol, Anjana Rao, João P. B. Viola. Characterization of the involvement of transcriptional repressor IRF2BP2 on T-cell proliferative response [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A87.