> Research
> Noriyuki Sato[TUMOR AND IMMUNOLOGY]
Our Department of pathology was established in 1945. Pathology is obviously a fundamental part of the medical school. Many doctors, scientists, graduate and undergraduate students have been participating in routine pathologic practice, research, education and social activities. The expertise and main field of our Department covers basic and clinical pathology, immunology, infection, oncology, cell biology and molecular biology. This broad interest constitutes fostering new ideas in research and links researchers of different background and fields of medicine and life science.
Our Department has focused on several interests, and each project has been dedicated to a fostering better understanding and advancement of pathology, immunology and medicine.
We analyzed the MHC class I-restricted human tumor antigens by using human autologous cytotoxic T lymphocytes (CTL) and tumor lines and tissues. We have studied tumor antigens by reverse-immunological and sophisticated bioinformatic approaches. Some of these antigens were entered into clinical trials since 2003 with many colleagues of clinical Departments and companies under the support from governments and private sources.
In these clinical trials, all patients have been periodically and carefully monitored by various immunological and patho-histological device. To this end we developed the world-first anti HLA-class I mAb that detect in patho-histological specimen.
Meanwhile, it has been requiring more sophisticated development for detecting native antigenic peptides complexed with HLA molecules. By using various ways, including phage library, artificial antibody interacting with these native epitope of vaccines is under exploitation.
The tumor immune-escape mechanism, particularly with focusing on epigenetic mechanism of the expression of MHC molecules, has also been studied, since such regulation is critically important in the tumor escape mechanism. To this end some of finding is now being applied in clinical trials.
Analysis of tumor antigens in“cancer stem cell/cancer-initiating cell”were begun in early 1980s in murine model, and recently we have successfully identified such tumor antigens in human cancer stem cell/cancer-initiating cell. These research may lead to understanding the nature of stem cell and establishing much more potent human cancer vaccine as well as very effective molecular targeting therapy.
HSP is considered to play an important role in immunology as well as cell biology. Immunologically it is suggested that HSP binds to antigenic peptides and controls the peptide translocation inside cells to MHC molecules. Our study also indicated exogeneously-pulsed HSP-peptide complexes, particularly HSP90, can enter antigen presenting cells via still-unknown cell surface receptor, and peptides could be cross-presented to CTL, resulting in the activation of these lymphocytes. This suggests that the HSP-peptide complex will become not only a potential cancer peptide vaccine strategy but effective vaccine in the infectious diseases.
HSP could also work in the apoptosis and degenerative process of the cells as the regulatory molecules. Particularly, we studied the regulatory function of certain HSP in the ER stress responses.
Our group also investigate new aspects of antigen processing by using proteomics approaches. This research will lead to understand the detail of intracellular peptide generation and natural peptide synthesis recognized by T cells.
We have been establishing anti-human lymphocyte antibody, designated as L series mAb. One of such mAb, L26, which reacts wit CD20 molecule in the pathological specimen, is very known as the standard world-wide mAb for diagnosing CD20 positive B cell malignancy. Meanwhile, recently it is indicating that L22 mAb specifically reacts to resting B cells of mantle zone of human tonsils. L22 detects arachidonate 5-lipoxygenase (ALOX5) and this molecule seems to play an important role in the maintenance of resting B cell phenotypes. These approaches will involve future immunobiological study of B cell development in connection with T follicular helper cells.
Our laboratory is studying various ranges of biomedical interests. Along with study, we will have new materials, like antibodies, and tools. Some of these can be applicable for potent new diagnostic method of human diseases, contributing development of molecular pathology.
