An Investigation into the Mechanisms of Memory Treg Cells in Restraining the Anti-Hepatoma Immune Responses

Accumulating evidence in recent years has clearly showed regulatory T cells (Treg cells) play an important role in protecting hepatoma from immune attack either on the stage of immune surveillance or when treating with anti-tumor immunotherapy. Therefore, an emerging notion about tumor immunotherapy developed recently is to curb the suppression effect of Treg cells in addition to evoke strong anti-tumor immune responses. From our preliminary data, we have shown a subgroup of Treg cells (memory Treg cells) that expressed a specific CCR5 increased in the process of losing concomitant anti-tumor immunity and possessed the ability to suppress the tumor-eradicating ability of CD8+T cells. Furthermore, the corresponding CCL5 was highly expressed by the tumor cell itself. Based on these results, we proposed a hypothesis that this subgroup of Treg cells (memory Treg cell) is the main player in subverting anti-tumor immune responses and the interaction venue is mainly within/around the tumor itself. Current proposal is aiming to characterize possible mechanisms of this subgroup of Treg cell in restraining the anti-tumor immune responses. We will achieve this goal by accomplish the following aims: (1) to define the characteristics of tumor–related memory Treg cells on anti-tumor immune responses; (2) to investigate the in vivo phenotypic and functional alterations of tumor-specific CD8+T cells under the impact of memory Treg cells in an animal model; (3) to investigate the relationship between tumor and tumor-protecting Treg cells; (4) to investigate the role of memory Treg cells in hepatoma patients and its relationship to anti-hepatoma immune responses. We expect these studies will provide invaluable information for developing effective strategies of tumor immunotherapy, especially emphasized on the inhibition of the suppression effect imposed by Treg cells.

Project ID:PC10005-0019
External Project ID:NSC100-3112-B182-001