2016 Kyoto Prize Laureates

Basic Sciences

Life Sciences and Medicine(Molecular Biology, Cell Biology, Systems Biology, etc.)

Tasuku Honjo

/  Medical Scientist

1942 -

Professor, Kyoto University

Commemorative Lectures

Serendipities of Acquired Immunity


11 /11 Fri

Place:Kyoto International Conference Center


From the Molecular Immunity to the Suppression of Cancer


11 /12 Sat

13:30 - 17:30

Place:Clock Tower Centennial Hall, Kyoto University

Achievement Digest

Discovery of the Mechanism Responsible for the Functional Diversification of Antibodies, Immunoregulatory Molecules and Clinical Applications of PD-1

Dr. Honjo has elucidated the mechanism for the functional diversification of antibodies by clarifying Class Switch Recombination and its responsible enzyme, AID. He also identified several important immunoregulatory molecules, including PD-1, whose function has led to the development of effective cancer immunotherapy. His discoveries and their clinical applications have significantly influenced research in the life sciences and medicine, resulting in eminent contributions to human welfare.

*This field then was Field of Life Sciences (Molecular Biology, Cell Biology, Neurobiology).


Antibodies, a major component of the immune system, are produced by B cells. The rearrangements of variable gene fragments of immunoglobulin (Ig) genes during the development of B cells in bone marrow provides antibodies binding activity to a vast variety of potential antigens. Upon activation by exposure to antigens and associated cytokine milieu in the secondary lymphoid tissues, B cells then produce antibodies of different classes such as IgM, IgA, IgG and IgE, which are different in biological functions and distribution on the body. Exposure to antigens also evokes somatic hypermutations (SHM) in the variable region, which confers higher binding affinity to particular antigens. However, how different classes of antibodies are produced and how SHM occurs remained long unknown.
In 1978, Dr. Tasuku Honjo proposed a class switch recombination (CSR) model of antibody class production, which he corroborated in subsequent works. According to this model, antibody class is determined by deleting a part of the immunoglobulin heavy chain gene and joining the region coding the corresponding class segment. He then established an in vitro model that recapitulates CSR using cultured B cells activated with interleukin (IL)-4, and cloned activation-induced cytidine deaminase (AID). Subsequent studies by his group proved that AID is not only responsible for CSR but also essential for SHM. Dr. Honjo thus identified the molecular mechanism underlying the generation of functionally divergent antibodies, thereby elucidating one of the basic principles of immunology.
In parallel with this study, Dr. Honjo cloned a variety of molecules that play important roles in immune responses. These include IL-4 and IL-5, which activate B cells and induce CSR; RBP-J kappa, which is a key mediator of Notch signaling in cell fate determination; and a chemokine SDF-1, which is important in hematopoietic niche formation in the bone marrow.
One of the molecules cloned by Dr. Honjo is PD-1, which negatively regulates the self-tolerance of the immune system, as evidenced by the development of various autoimmune diseases after deletion of this gene as well as suppression of T cell activation by binding to its specific ligand PD-L1. Based on these findings, Dr. Honjo and his colleagues administered anti-PD-L1 antibodies in mice bearing PD-L1-expressing tumors and found that blocking the PD-1-PD-L1 binding significantly inhibited tumor growth and prolonged survival. This milestone discovery by Dr. Honjo stimulated the development of anti-PD-1 and anti-PD-L1 antibodies as anti-cancer immunotherapeutic agents. Subsequent large-scale clinical trials using the humanized anti-PD-1 antibody demonstrated marked efficacy against various cancers in humans and the antibody drug is now in clinical use in Japan, the U.S., and Europe.
Dr. Honjo has thus contributed to basic science by clarifying the mechanism responsible for the functional diversification of antibodies, one of the basic principles of immunology, and by identifying several important immunoregulatory molecules. His identification of PD-1/PD-L1 and their function has led to the development of effective cancer immunotherapy contributing significantly to human health and welfare.
For these reasons, the Inamori Foundation is pleased to present the 2016 Kyoto Prize in Basic Sciences to Dr. Tasuku Honjo.


Born in Kyoto City, Japan
M.D. Faculty of Medicine, Kyoto University
Ph.D. in Medical Chemistry, Kyoto University
Fellow, Department of Embryology, Carnegie Institution of Washington
Visiting Fellow and Associate, National Institute of Child Health and Human Development, National Institutes of Health
Assistant Professor, Faculty of Medicine, The University of Tokyo
Professor, Graduate School of Medicine, Osaka University
Professor, Graduate School of Medicine, Kyoto University
Professor, School of Medicine, Hirosaki University
Professor Emeritus, Kyoto University
Chairman of the Board, Shizuoka Prefectural University Corporation
President, Foundation for Biomedical Research and Innovation
Selected Awards and Honors
Noguchi Hideyo-Memorial Award for Medicine
Erwin von Balz Prize, Boehringer Ingelheim
Takeda Medical Prize
Uehara Prize
The Imperial Prize and the Japan Academy Prize
Order of Culture, Government of Japan
Tang Prize
William B. Coley Award for Distinguished Research in Basic and Tumor Immunology, Cancer Research Institute
Richard V. Smalley, MD Memorial Award, Society for Immunotherapy of Cancer
Leopoldina, National Academy of Sciences, The American Association of Immunologists, The Japan Academy

Profile is at the time of the award.

Related Videos