The discovery of a large array of
tumor antigens has demonstrated that host lymphocytes can indeed recognize and destroy
tumor cells as originally proposed in the
cancer immunosurveillance hypothesis. Recent reports that led to the
cancer immunoediting concept also strongly support the immunosurveillance hypothesis, and they further indicate that the host immune system plays a critical role not only in promoting host protection against
cancer but also in selecting
tumors that can better escape from immune attack. Thus, it is now clear that T cells have the ability to recognize and destroy spontaneously arising
tumors. However, the generation of antitumor immunity is often difficult in the
tumor-bearing host because of various negative regulatory mechanisms. Here, we review our recent work on
tumor immunotherapy, which utilizes the activation of type-1 innate and/or acquired immunity as a potent strategy to overcome immunosup-pression in the
tumor-bearing host. We have established a variety of
tumor therapeutic protocols that aim to activate type-1 immunity, such as
tumor-vaccine therapy with CpG encapsulat-ed in
liposomes,
cell therapy using
tumor-specific Th1 cells, and gene therapy using gene-engineered Th1 cells. We found that CpG encapsulated in
liposomes stimulated IL-12-producing DC and induced IFN-gamma-producing NK cells, NKT cells, and
tumor-specific CTL. Th1 cell
therapy was also shown to be beneficial for acceleration of APC/Th1 cell-cell interaction in the DLN, which was critical for inducing
tumor-specific CTL at the
tumor site. Therefore, we conclude that the activation of type-1 innate and acquired immunity is crucial for
tumor immunotherapy in order to overcome strong immunosuppression in the
tumor-bearing host.