Defining the Role of BTLA in Breast Cancer Immunosurveillance and Selective Targeting of the BTLA-HVEM-LIGHT Costimulatory System
Annual rept. 1 May 2009-30 Apr 2010
WASHINGTON UNIV ST LOUIS MO
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The current reporting period represents approximately the first year of the 2 year award. During the first year the primary goals of generating crosses between various genetic strains of mice were initiated and are currently underway, with the bulk of the proposed analysis awaiting completion of this phase. However, in addition during this period we have undertaken mechanistic studies of the actions of BTLA in regulating immune responses, and have uncovered a beneficial mechanism whereby graph vs host disease is prevented by administration of anti-BTLA antibodies at the time of bone marrow transplantation. While we continue in the proposed tasks related to generation of breast cancer mouse models, we are encouraged at the therapeutic benefit of BTLA directed therapy in the murine GVHD paradigm. Mechanistic discoveries should apply across various model systems in which BTLA and its interactions with its ligands are manipulated. Our current mechanistic investigations into the GVHD effect indicate that anti-BTLA antibody treatment operates through a selective reduction in the expansion of autoreactive effector T cells compared to the expansion of regulatory T cells during the period of lymphopenic expansion. Thus in essence, therapy directed at BTLA in this model allows the appropriate expansion of T reg cells that are able then to control a reduced number of autoreactive effector T cells.
- Medicine and Medical Research