I am Hiroyoshi Nishikawa, and I have been appointed as a professor at the Division of Cancer Immune Multicellular System Regulation, Center for Cancer Immunotherapy and Immunology, Kyoto University Graduate School of Medicine, as of July 2024.

I graduated from Mie University School of Medicine in 1995, and after three years of clinical training, I entered the Mie University Graduate School of Medicine in 1998. I started tumor immunology research under Professor Hiroshi Shiku (at that time) and conducted basic research to establish a new cancer immunotherapeutic strategy by augmenting antitumor immune responses in animal models. In particular, I pursued a strategy to induce efficient activation of CD8+ T cells by modulating CD4+ helper T cells. Then, I found that CD4+ T cell activation was controlled by the recognition of highly immunogenic selfantigens derived from cancer cells. After completing my thesis study, I continued this research theme and elucidated that the same antigen was also recognized by CD4+ regulatory T (Treg) cells and that inflammatory cytokines in the local lesion controlled the balance of CD4+ T cell responses to the same antigen.

I then moved to the Memorial Sloan Kettering Cancer Center (Dr. Lloyd J. Old’s lab) in the U.S., where I expanded my research from animal models to humans. At that time, Dr. Old told me the importance of conducting research in humans in the cancer immunology field. I found that T cell responses to NY-ESO-1 antigen, one of the most clinically applied cancer/testis antigens in the world at that time, were suppressed by Treg cells. In addition, the immunosuppression by Treg cells was overwhelmed by employing bacteria (Salmonella) as an antigen delivery system. These studies on cancer immunosuppression by Treg cells provided me an opportunity to continue my research with Professor Shimon Sakaguchi in Immunology Frontier Research Center (IFReC), Osaka University, who discovered Treg cells. In the Sakaguchi’s Laboratory, I investigated the immunosuppressive mechanism from the suppressed side (i.e., cancer antigen-specific CD8+ T cells) by Treg cells. CD8+ T cells that responded to self-derived cancer antigens (so-called shared antigens) fell into a characteristic anergy state by suppression of Treg cells, and elucidated the nature of the anergic T cells, which has been a longstanding conundrum in immunology. On the other hand, this immunosuppressive phenotype was not observed in CD8+ T cells against foreign antigens (so-called neo antigens).

Since April 2015, I have been in charge of the Division of Cancer Immunology, Research Institute/Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center Japan, and since April 2016, I have had a cross appointment in the Department of Immunology, Nagoya University Graduate School of Medicine. I have been given a very challenging, but rewarding position to conduct a wide range of research, from basic to translational research, on issues related to cancer immunotherapy, which is now being applied clinically. In particular, by focusing on the tumor microenvironment, where cancer cells and immune cells directly confront each other, my team tries to elucidate the immunosuppressive mechanisms in the tumor microenvironment to develop cancer immunotherapy that can augment antitumor immune responses to gain clinical efficacy. It is a great pleasure and a great challenge for me to be able to pursue my research under the guidance of Dr. Tasuku Honjo, the 2018 Nobel Prize winner in Physiology or Medicine, at the Center for Cancer Immunotherapy and Immunology, where he is the Director.

With the clinical application of cancer immunotherapy, research focusing on the diversity of cancer cells, tumor microenvironment, and individual patients is becoming increasingly important. I have been conducting research that challenges the diversity of humans by establishing a novel research style from human to animal models, in which integrated analysis combining comprehensive immunological analysis and genome analysis (immune-genomic analysis) is introduced into human cancer immunology research, and the findings are applied to animal models to clarify the universal significance of the findings. Then, I have proposed a new hypothesis in cancer biology, the “immune-genomic cancer evolution” which proposes that genomic abnormalities in cancer cells directly affect the surrounding immune system and generate an immunosuppressive microenvironment. In the future, I would like to further develop my research to understand immune responses as a dynamic phenomenon involving a wide variety of cells. From the microbiological perspective of molecular expression and spatio-temporal dynamics of a single cell, as well as from a macrobiological perspective at the tissue and individual level, changes in intercellular networks are elucidated. Then, how immunosuppressive mechanisms in the tumor microenvironment are established during carcinogenesis to cancer progression is comprehensively explored from multiple perspectives, including immunity, epigenome, genome, and metabolism, and mathematical models. I would like to expand our research to precision medicine and even preventive medicine. I look forward to your continued guidance and encouragement in Kyoto University.