Immunotherapy of Cancer by Targeting Regulatory T cells.

Regulatory T (Treg) cells maintain immune homeostasis by inhibiting abnormal/overactive immune responses to both autogenic and nonautogenic antigens. Treg cells play an important role in immune tolerance, autoimmune diseases, infectious diseases, organ transplantation, and tumor diseases. Treg cells have two functional characteristics: T cell anergy and immunosuppression. Treg cells remain immune unresponsive to high concentrations of interleukin-2 and anti-CD3 monoclonal antibodies. In addition, the activation of Treg cells after TCR-mediated signal stimulation inhibits the activation and proliferation of effector T cells. In the process of tumor development, Treg cells accumulate locally in the tumor and lead to tumor escape by inducing anergy and immunosuppression. It is believed that targeted elimination of Treg cells can activate tumor-specific effector T cells and improve the efficiency of cancer immunotherapy. Therefore, inhibition/clearance of Treg cells is a promising strategy for enhancing antitumor immunity. Here, we review studies of cancer immunotherapies targeting Treg cells.

The functions of EZH2 in immune cells: Principles for novel immunotherapies.

Enhancer of zeste homolog 2 (EZH2) is aberrantly expressed or mutated in multiple types of cancer cells and plays an oncogenic role in tumorigenesis and development in most cancers. Results from pilot clinical studies have implied that EZH2 inhibitors have therapeutic potential against some cancers. However, the exact mechanisms by which EZH2 plays oncogenic roles and EZH2 inhibition exerts anticancer effects are incompletely understood. To date, the findings of studies focusing on EZH2 and cancer cells have failed to fully explain the observations in preclinical and clinical studies. Therefore, recent studies about the roles of EZH2 in cancers have shifted from cancer cells to immune cells. The human immune system is a complex network comprising multiple subpopulations of immune cells. Immune cells communicate and interact with cancer cells during cancer development and treatment, dictating the fate of cancer cells. Elucidating the roles of EZH2 in immune cells, especially in cancer patients, promises the identification of novel immunotherapeutic strategies or priming of existing immunotherapies against cancer. Hence, we reviewed the studies focusing on the involvement of EZH2 in various immune cells, aiming to provide ideas for immunotherapies targeting EZH2 in immune cells.