Tasuku Honjo

Tasuku Honjo
Born	27 1, 1942
Birthplace	Kyoto, Japan
Nationality	Japanese
Occupation	Physician-scientist, immunologist
Employer	Kyoto University
Known for	Discovery of PD-1 (programmed cell death protein 1), identification of IL-4, IL-5, and activation-induced cytidine deaminase (AID)
Education	Kyoto University (BS, MD, PhD)
Awards	Nobel Prize in Physiology or Medicine (2018), Tang Prize in Biopharmaceutical Science (2014), Kyoto Prize (2016)
Website	[https://kuias.kyoto-u.ac.jp/e/profile/honjo/ Official site]

Tasuku Honjo (本庶 佑, Honjo Tasuku; born January 27, 1942) is a Japanese physician-scientist and immunologist whose research fundamentally altered the understanding of immune regulation and opened new frontiers in the treatment of cancer. Working for decades at Kyoto University, Honjo identified programmed cell death protein 1 (PD-1), a receptor on the surface of T cells that functions as an immune checkpoint — effectively serving as a "brake" on the immune system's ability to attack cells, including tumor cells. His discovery led to the development of a class of cancer immunotherapy drugs known as PD-1 inhibitors, which have demonstrated effectiveness against multiple types of cancer and have been adopted in clinical oncology worldwide. In 2018, Honjo was jointly awarded the Nobel Prize in Physiology or Medicine alongside American immunologist James P. Allison, who independently discovered another immune checkpoint mechanism involving CTLA-4. Beyond PD-1, Honjo is recognized for his molecular identification of cytokines IL-4 and IL-5, as well as the discovery of activation-induced cytidine deaminase (AID), an enzyme essential for class switch recombination and somatic hypermutation in antibody diversification. He has been elected a foreign associate of the National Academy of Sciences of the United States, a member of the German Academy of Natural Scientists Leopoldina, and a member of the Japan Academy.

Early Life

Tasuku Honjo was born on January 27, 1942, in Kyoto, Japan. He grew up in the culturally rich environment of Kyoto, a city that has long been associated with Japan's academic and scientific traditions. Honjo has described his early years and intellectual development in various interviews, noting the influence that the academic atmosphere of Kyoto had on his decision to pursue medicine and science.

Growing up in postwar Japan, Honjo came of age during a period of rapid modernization and scientific advancement in the country. His interest in biology and medicine developed during his formative years, and he chose to pursue a career that would combine clinical medicine with fundamental research. He entered Kyoto University, one of Japan's most prestigious institutions, which would become his intellectual home for virtually his entire career.

Education

Honjo received his education entirely at Kyoto University, earning his Bachelor of Science degree, his Doctor of Medicine (MD) degree, and his Doctor of Philosophy (PhD) degree from the institution. His graduate research focused on molecular biology and immunology, fields that were undergoing rapid expansion during the 1960s and 1970s as new techniques in molecular biology allowed scientists to investigate the genetic and molecular mechanisms underlying immune function.

After completing his doctoral work at Kyoto University, Honjo pursued postdoctoral research in the United States, a common path for ambitious Japanese scientists of his generation who sought to broaden their training in the leading laboratories of the world. This period of international training proved formative for his later research career, exposing him to cutting-edge techniques in molecular biology and immunology that he would later apply to his groundbreaking studies on immune regulation.

Career

Early Research and Cytokine Identification

Honjo's early career established him as a significant figure in the field of molecular immunology. Working at Kyoto University, he made fundamental contributions to the understanding of the molecular mechanisms that govern immune cell function. Among his most important early achievements was the molecular identification of the cytokines IL-4 and IL-5, signaling molecules that play critical roles in regulating immune responses. IL-4 is involved in the differentiation of T helper cells and the activation of B cells, while IL-5 plays a key role in the growth and differentiation of eosinophils. The molecular characterization of these cytokines provided essential tools for researchers seeking to understand the complex signaling networks that coordinate immune responses.

Honjo also made a major contribution to understanding the molecular basis of antibody diversity through his discovery of activation-induced cytidine deaminase (AID). This enzyme was shown to be essential for two critical processes in B cell biology: class switch recombination, which allows B cells to switch the type of antibody they produce (for example, from IgM to IgG), and somatic hypermutation, which introduces point mutations into antibody genes to generate higher-affinity antibodies. The discovery of AID provided a unified molecular explanation for these two seemingly distinct processes and represented a fundamental advance in the understanding of adaptive immunity. This work established Honjo's laboratory as one of the leading centers for molecular immunology research in the world.

Discovery of PD-1

The discovery for which Honjo is most widely known — the identification of programmed cell death protein 1 (PD-1) — came in 1992, when his laboratory at Kyoto University identified the gene encoding PD-1 through a subtractive hybridization screen designed to find genes involved in programmed cell death. The protein, expressed on the surface of activated T cells, was initially studied in the context of apoptosis, but subsequent research by Honjo and his colleagues revealed that PD-1 functions as a negative regulator of immune responses — an immune checkpoint.

Through a series of meticulous experiments conducted over many years, Honjo's group demonstrated that PD-1, when engaged by its ligands PD-L1 and PD-L2, delivers an inhibitory signal to T cells that dampens their ability to attack target cells. Under normal physiological conditions, this mechanism serves a vital function in preventing autoimmunity — ensuring that the immune system does not destroy the body's own healthy tissues. However, Honjo and his team recognized that tumors could exploit this pathway, expressing PD-L1 on their surface to essentially hide from the immune system by engaging PD-1 on tumor-infiltrating T cells and switching off the immune attack.

This insight — that blocking the PD-1 pathway could release the immune system's brakes and allow T cells to attack cancer cells — became the foundation for a new class of cancer immunotherapy drugs. Animal experiments conducted in Honjo's laboratory showed that blocking PD-1 with antibodies could lead to tumor regression in mice, providing proof of concept for what would become one of the most significant therapeutic strategies in modern oncology.

Development of Cancer Immunotherapy

The translation of Honjo's basic research discoveries into clinical cancer treatments represents one of the most impactful bench-to-bedside stories in recent medical history. Based on the mechanistic understanding provided by Honjo's work, pharmaceutical companies developed monoclonal antibodies that block PD-1 or its ligand PD-L1, thereby removing the inhibitory signal and allowing the patient's own immune system to recognize and destroy cancer cells.

The resulting drugs, including nivolumab (marketed as Opdivo) and pembrolizumab (marketed as Keytruda), have been approved for the treatment of numerous cancer types, including melanoma, non-small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, and many others. Clinical trials demonstrated that these PD-1 inhibitors could produce durable responses in a significant fraction of patients, including some with advanced cancers that had previously been considered untreatable.

The development of PD-1 inhibitors occurred in parallel with work by James P. Allison on CTLA-4, another immune checkpoint molecule. While the two researchers worked independently and on different molecular targets, their discoveries were conceptually complementary: both demonstrated that the immune system possesses "brakes" that can be released to fight cancer. The combined insights from their work established the field of immune checkpoint therapy as a pillar of modern cancer treatment.

Honjo's work on PD-1 led to a collaboration with the Japanese pharmaceutical company Ono Pharmaceutical, which was involved in the development of nivolumab. This collaboration would later become the subject of a significant legal dispute over royalties (see below).

Academic Positions at Kyoto University

Throughout his career, Honjo maintained his primary academic affiliation with Kyoto University, where he served in various capacities within the university's medical and scientific community. He led the Department of Immunology and Genomic Medicine and became affiliated with the Center for Cancer Immunotherapy and Immunobiology (CCII) at Kyoto University. He also became a Distinguished Professor at the Kyoto University Institute for Advanced Study (KUIAS), where he continued his research into immune regulation and its applications.

Among his notable students was Shizuo Akira, who went on to become a prominent immunologist in his own right, known for his research on innate immunity and toll-like receptors. The mentorship of students and younger researchers has been an important aspect of Honjo's contribution to the field of immunology.

Ongoing Research

Even after receiving the Nobel Prize, Honjo continued active research at Kyoto University. His laboratory has pursued further investigations into the PD-1 pathway, including studies on how age-related changes in the immune system affect the efficacy of PD-1 blockade therapy. A 2025 publication from his group examined age-related immune states and their implications for PD-1 blockade, seeking to develop strategies to improve immunotherapy outcomes in elderly patients — a clinically important question given that cancer incidence increases with age.

Legal Dispute with Ono Pharmaceutical

In June 2020, Honjo announced his intention to sue Ono Pharmaceutical, the Osaka-based pharmaceutical company that had been involved in the development and commercialization of the PD-1 inhibitor nivolumab (Opdivo). Honjo stated that he believed he was owed approximately 22 billion yen (approximately $200 million) in royalties from the drug's commercial success. The dispute centered on the terms of the licensing agreement between Honjo and Ono Pharmaceutical regarding the intellectual property arising from his PD-1 research.

The case attracted significant attention in both Japan and the international scientific community, raising broader questions about how academic researchers are compensated when their basic science discoveries lead to commercially successful pharmaceutical products. Honjo indicated that he intended to donate a substantial portion of any settlement to support young researchers.

In November 2025, the dispute was resolved when Honjo won a major settlement with Ono Pharmaceutical, according to reporting by the Asahi Shimbun. The settlement brought to a close a long-running legal battle over royalties following his discovery of PD-1.

Personal Life

Honjo has maintained a relatively private personal life throughout his career. In his Nobel Prize interview, he reflected on the moment he learned of the award, describing how the first communication he received was from another foundation before receiving official notification from the Nobel Committee. He has spoken publicly about his dedication to basic research and the importance of curiosity-driven science, emphasizing that the clinical applications of his PD-1 discovery were not the original motivation for the research but rather emerged from a commitment to understanding fundamental biological mechanisms.

Honjo has expressed a strong commitment to supporting the next generation of scientists. Following his Nobel Prize win, he indicated a desire to use a portion of his prize money and any royalty income to establish funding for young researchers in Japan, reflecting his concern about maintaining the country's scientific competitiveness.

He has maintained his residence in the Kyoto area throughout most of his career, remaining closely associated with Kyoto University and its broader academic community.

Recognition

Tasuku Honjo's contributions to immunology and medicine have been recognized with numerous awards and honors spanning several decades.

In 1989, he received the Asahi Prize, one of Japan's premier awards for academic and cultural achievement. He was elected as a foreign associate of the National Academy of Sciences of the United States in 2001, a member of the German Academy of Natural Scientists Leopoldina in 2003, and a member of the Japan Academy in 2005.

Honjo received the Robert Koch Prize from the Robert Koch Foundation in Germany, recognizing his contributions to biomedical science.

In 2014, Honjo and James P. Allison were jointly awarded the Tang Prize in Biopharmaceutical Science, recognizing their respective discoveries of immune checkpoint mechanisms and the therapeutic potential of checkpoint blockade in cancer treatment.

In 2016, he was awarded the Keio Medical Science Prize by the Keio University Medical Science Fund. That same year, he received the Kyoto Prize in Basic Sciences, awarded by the Inamori Foundation for outstanding contributions to the scientific, cultural, and spiritual betterment of humankind.

In 2017, Honjo received the Warren Alpert Foundation Prize from Harvard Medical School, which recognizes scientists whose work has improved the understanding, prevention, treatment, or cure of human disease.

He was named a Clarivate Citation Laureate in 2018, identified as a researcher whose citation impact indicated Nobel-class research.

The crowning recognition of his career came on October 1, 2018, when the Nobel Assembly at Karolinska Institutet awarded the Nobel Prize in Physiology or Medicine jointly to Honjo and James P. Allison "for their discovery of cancer therapy by inhibition of negative immune regulation." The Nobel Committee noted that the laureates' work had "established an entirely new principle for cancer therapy" by showing that the strategy of stimulating the inherent ability of the immune system to attack tumor cells could be harnessed therapeutically.

Honjo also received the Order of Culture from the Japanese government and has been honored by Osaka University with recognition for his contributions to science.

He was also awarded the Imperial Prize and Japan Academy Prize, recognizing his outstanding contributions to Japanese scholarship.

Legacy

Tasuku Honjo's identification of PD-1 and the subsequent development of PD-1 inhibitor therapies represents one of the most consequential advances in cancer treatment of the early 21st century. Before the advent of immune checkpoint therapy, the standard approaches to cancer treatment — surgery, chemotherapy, and radiation — had limited effectiveness against many advanced cancers. The demonstration that the immune system could be harnessed to fight cancer by removing inhibitory checkpoints opened an entirely new therapeutic paradigm.

PD-1 inhibitors have been approved for use in dozens of cancer types and have extended the lives of hundreds of thousands of patients worldwide. For some cancers, including advanced melanoma and certain lung cancers, PD-1 blockade has transformed the prognosis from uniformly fatal to potentially curable in a subset of patients. The success of PD-1 therapy has also spurred an enormous research effort into identifying biomarkers that predict which patients will respond to checkpoint therapy, developing combination therapies that enhance response rates, and discovering additional immune checkpoints that might serve as therapeutic targets.

Honjo's earlier work on AID and class switch recombination also remains foundational to the field of B cell biology and continues to influence research on antibody engineering and the molecular basis of immune diversification.

Through his mentorship of students such as Shizuo Akira and his long tenure at Kyoto University, Honjo has also contributed to building Japan's capacity in immunological research. His legal dispute with Ono Pharmaceutical, while contentious, drew attention to important questions about the relationship between academic discovery and pharmaceutical commercialization, and about the fair compensation of scientists whose basic research leads to billion-dollar therapeutic products.

The Nobel Committee's decision to recognize Honjo and Allison together reflected the complementary nature of their discoveries: two independent researchers, working on different molecules in different countries, converged on the same fundamental insight — that the immune system's internal braking mechanisms could be therapeutically manipulated to fight cancer. This principle, now known as immune checkpoint therapy, has become a cornerstone of modern oncology and continues to evolve as researchers build upon the foundations laid by Honjo and his colleagues.