Research on human
tumor immunology has greatly advanced in the past two decades. Many immunogenic
tumor antigens have been identified, and some of these
antigens entered in clinical trials. Consequently, it has been shown that these
antigens can inhibit
tumor growth in patients to some extent, indicating that they act as potent immunogenic therapeutic
vaccines in
cancer patients with
malignancies originating from various tissues. These patients had
antigen-specific cytotoxic T-lymphocyte (CTL) responses when assessed on tetramer,
enzyme-linked immunospot (ELISPOT), T-cell clonotype and CTL induction efficiency. Thus, it has become clear that human
tumor vaccines can evoke clinical and immunological anti-
tumor responses in patients. The
tumor regression effects of
tumor vaccines, however, are generally low, and it is obvious that current vaccination protocols are generally too weak to provide substantial and satisfactory clinical benefits. This means that other drastic and more potent clinical and immunological protocols are required in
cancer immunotherapy. To find such efficient protocols the basic immunological and
biological properties of
cancers must be investigated. In the present review the identification of human
tumor antigens recognized on CTL and the clinical trials are introduced. Next, the most recent analysis of human
cancer-initiating cell (cancer stem cell)-associated
antigens is described. These
antigens might be able to act as 'universal, general and fundamental'
tumor antigens. Also present is the authors' recent study for increasing cross-presentation efficiency in dendritic cells and subsequent enhancement of
human leukocyte antigen (HLA)-class I-restricted
peptide antigenicity by using HSP90 and ORP150
molecular chaperones that act as endogenous
Toll-like receptor ligands. In addition to the aforementioned manipulation of the positive loop of
tumor immunity, it is necessary to regulate and intervene in the negative loop. In particular, the potential of the expression of HLA class I molecule regulation by epigenetic mechanisms will be discussed. Finally, the type of basic and clinical
tumor immunology research highly required currently, and in the very near future, are described.