Previously, the field of tumor immunology has relied on T cell receptor (TCR) transgenic mice and model tumor antigens to study the T cell and tumor cell interaction. However, these models have limitations. Namely, they do not reflect the natural affinity or precursor frequency of tumor antigen specific T cells. Recently, a novel Nur77GFP mouse was generated that allows us to study the antigen receptor signal strength and study the tumor immune response to endogenous tumor antigens. This mouse has a green fluorescent protein regulated by antigen receptor signaling. The stronger the antigen:antigen receptor interaction, the higher the Nur77GFP. Importantly, the reporter is sensitive to even very weak antigen receptor engagement as is speculated to be the nature of endogenous tumor antigens. Our preliminary data suggests that the co-expression of Nur77GFP and PD-1 identifies a subpopulation of polyclonal endogenous tumor infiltrating lymphocytes that are exclusively tumor antigen specific; produce more IFNγ upon re-stimulation with syngeneic tumors, and increases with anti-OX40 therapy. We have previously shown that treatment of tumor bearing hosts with anti-0X40 can promote tumor regression, therefore we propose that one mechanism of OX40 mediated immunotherapy is via the expansion of high affinity tumor antigen specific T cells within the tumor microenvironment.
- Copyright © 2013 by The American Association of Immunologists, Inc.