| 研究実績の概要 |
We have demonstrated in the past that “CTLA-4” is a molecule that is critical for Treg function especially in the context of autoimmune disease. In this project, we reasoned that its expression on Treg cells may also promote negative changes antigen-presenting cells (APCs) in the tumor tissue. First, we evaluated the expression levels of CTLA-4 and found that compared to the Tregs in other tissues, the Treg cells in the tumor have substantially higher amount of CTLA-4 on their surface. Since CTLA-4 can negatively affect the appearance and function of antigen-presenting cells, we also checked whether there are differences in these cells in tumors with high or low Treg cells. Antigen-presenting cells within tumors with high Treg cells expressed lower levels certain costimulatory molecules compared to mice with much reduced Treg fractions arising from depletion. In support of this observation, APCs from the tumors with high Treg cells showed poor ability to initiate T cell response compared to APCs from tumors lacking Treg cells.
Lastly, we checked whether Treg cells from tumors can induce an abnormal appearance on T cells when tested in tissue culture. Indeed, tumor-Treg cells promoted increased expression of a number of proteins associated with impaired function on the surface of T cells that were cultured with the Treg cells.
Overall, our findings provide potential explanation for how Treg cells may promote T cell dysfunction in the tumor. Thus, therapies that can disrupt Treg function in the tumor should hold promise for treating cancer.
|
