Defining the Role of BTLA in Breast Cancer Immunosurveillance and Selective Targeting of the BTLA-HVEM-LIGHT Constimulatory System

The current reporting period represents the second year of the award. In the first year the primary goals of generating crosses between various genetic strains of mice were initiated. In the repost for the first year, described the discovery of a use for BTLA that could be applied to treatment of breast cancer in an unanticipated manner. One therapy used to treat metastatic breast cancer is autologous stem cell transplantation, or bone marrow transplantation BMT, which however can cause serious or even lethal graft versus host disease GvHD. GvHD therefore presents a real limitation to the use of BMT in treating metastatic breast cancer. In our previous report, we described our discovery that administration of anti-BTLA antibodies at the time of bone marrow transplantation permanently prevent GvHD in murine models. In the second year, we pursued to determine the mechanistic basis for this effect. This work was very successful, and we have now published our study in the Journal of Experimental Medicine.