My favorite phrase: What is new today?

Q: Why did you choose this phrase?

When I was studying immunology at Memorial Sloan Kettering Cancer Center, I had to give a progress report at the end of each day, starting with the title word from Dr. Lloyd J. Old, the head of the laboratory. This puts me under a lot of pressure, which at the time, I found very difficult. However, it was a very important opportunity for me to summarize my data of the day and think about the next experiment, and it has become an important routine for me to consider my daily data and the future development of my research. At that time, however, I had a hard time producing data and was nicknamed "Dr. Not-yet."

Q: What is your research topic?

I am analyzing the immune tolerance mechanism (the mechanism by which the immune system reacts to foreign substances (non-self) but not to self) through research to clarify how the immune response to cancer is regulated. Among the cells involved in immune tolerance, we are focusing on regulatory T cells to study their involvement in the immune response to cancer, and promoting its application to cancer immunotherapy. Through the research, I would like to clarify the regulatory mechanisms of immune tolerance (not reacting against self) and immune surveillance (reacting against non-self), which are the basis of immune responses, and to elucidate the pathogenesis of a wide range of diseases including cancer.

Q: What will this research enable us to do?

The immune system is a mechanism that eliminates foreign substances such as viruses and bacteria from the body. Recent studies have revealed that the immune system is involved in almost all diseases including cancer and atherosclerosis. Clarifying the regulatory mechanism of immune response will elucidate the true nature of diseases and lead to the development of new treatment strategies. It is still fresh in our minds that immunotherapy has been clinically applied to cancer and was selected for the 2018 Nobel Prize in Physiology or Medicine.

Q: How did you embark on this research?

After graduating from medical school and clinical training, I practiced hematology/oncology. I treated many cancer patients daily, but unfortunately, the treatments were rarely successful. Therefore, I wanted to develop a more effective cancer treatment with fewer side effects, and started studying cancer. I learned from Professor Shiku in my department that immune responses are induced against cancer, and realized that the regulatory mechanism of immune responses against cancer was not fully understood. Thus, I started working on immunology, especially cancer immunology.

Q: When do you realize that research is interesting or rewarding?

When I am conducting research and come across unexpected experimental results, I feel that research is interesting: When I was a graduate student, I was studying the strategies to strengthen T cells, which destroy cancer cells, to treat cancer. However, to the contrary, the reagent I injected into the mice to augment the T cell functions worsened the cancer. This result was unexpected, but no matter how many times it was repeated, the cancer worsened. Then, we studied the mice that had been treated with the reagent in detail and found that the reagents had enhanced the regulatory T cells involved in immune tolerance. This led me to continue my research on regulatory T cells (for more than 20 years). This type of serendipity is one of the most exciting and interesting aspects of my research.

Q: I heard that you have a close relationship with Dr. James P. Allison, who was awarded the Nobel Prize in Physiology or Medicine this year (2018). Could you tell us about this?

Dr. James P. Allison, who won the Nobel Prize in Physiology or Medicine, was the head of the laboratory next to mine on the same floor at Memorial Sloan Kettering Cancer Center, where I studied. Dr. Allison was a very friendly researcher, and he often invited young researchers like me from the next lab over for lunch, where we had a great time discussing research. This was around when clinical trials targeting CTLA-4, which was the subject of the Nobel Prize in Physiology or Medicine, were being launched, and we discussed the role of CTLA-4 in the regulatory T cells I was studying.

Q: Please tell us about an experience that you can only talk about now.

At Memorial Sloan Kettering Cancer Center, where I studied abroad, one clinical fellow from the Division of Urologic Oncology in Dr. Lloyd J. Old's laboratory (Dr. Padmanee Sharma) had a very lively discussion with Dr. James P. Allison. That person later became Dr. Allison's wife.

Q: What are your goals and ambitions for the future?

I would like to understand the regulatory mechanisms of immune responses involved in various diseases and elucidate the relationship between individual life phenomena and diseases. Currently, I am studying the immune response to cancer, but I would like to clarify the true nature of more diseases and develop new effective treatment strategies.