Regulatory T cells (Tregs) play important roles in the maintenance of immune homeostasis, and is also involved in tumor immune tolerance. Dampening or elimination of Treg functions has been shown to lead to enhanced immune responses against tumors, and thus inhibition of tumor growth. Recently, we have developed a new immunization scheme, referred to as irradiated mitogen-activated autologous T cell vaccination (ATCV), and shown that such immunization could significantly enhance anti-tumor immunity in vivo. Mechanistically, the enhanced anti-tumor response appears to be due to reduced Treg functions and inhibition of activation-induced cell death (AICD) in effector T cells. Thus, ATCV may constitute a novel strategy in cancer immune therapy.