AAI Members Awarded the 2018 Nobel Prize
in Physiology or Medicine

AAI congratulates American immunologist James P. Allison (AAI ’78) and Japanese immunologist Tasuku Honjo (AAI ’88) on being awarded the 2018 Nobel Prize in Physiology or Medicine for pioneering research that led to novel approaches of cancer treatment. The committee said the scientists’ research – “which harnesses the body's immune system to attack cancer cells – amounted to a landmark in our fight against cancer.” Their approach had “revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed.” In an opening statement with MD Anderson after the announcement, Allison said “I’m honored and humbled to receive this prestigious recognition. A driving motivation for scientists is simply to push the frontiers of knowledge. I didn’t set out to study cancer but, rather, to understand the biology of T cells; these incredible cells travel throughout our bodies and work to protect us.”

Dr. Allison is Professor and Vivian L. Smith Distinguished Chair of the Department of Immunology, Executive Director of the Immunotherapy Platform at The University of Texas MD Anderson Cancer Center, and Co-Director of the Parker Institute for Cancer Immunotherapy. He is also Deputy Director of the Koch Center for Applied Research of Genitourinary Cancers at MD Anderson.

Allison served as AAI President (2001–2002), and as a member of the AAI Council (1996–2003). He also served as an Associate Editor and Section Editor for The Journal of Immunology (1987–1996), as a member of the AAI Committee on Public Affairs (1995–1997), and as an Abstract Programming Chair (1994–1997). Allison has been a frequent and popular speaker at the AAI annual meetings as a Major Symposia chair and speaker, and he was selected as a Distinguished Lecturer for the 1993 meeting. He was honored by AAI with the AAI-Dana Foundation Award for Human Immunology Research in 2008, and received in 2011 the Lifetime Achievement Award – the highest honor awarded to AAI members.

The 2018 Nobel Prize recognizes Allison’s work on the inhibitory effect of CTLA-4 on T cell activation and later research that showed that using an antibody against CTLA-4 released this inhibition and enabled T cells to kill tumors.

According to NIH Director Dr. Francis S. Collins, “Jim’s work was pivotal for cancer therapy by enlisting our own immune systems to launch an attack on cancer and arrest its development. NIH is proud to have supported this groundbreaking research.” Dr. Allison has received continuous funding from NIH since 1979, receiving more than $13.7 million primarily from the National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID). NIAID Director and AAI member Dr. Anthony S. Fauci (AAI ’73) said, “Dr. Allison’s elegant and groundbreaking work in basic immunology over four decades, and its important applicability to cancer, is a vivid demonstration of the critical nature of interdisciplinary biomedical research supported by NIH.”

For his part, Dr. Honjo mirrored the sentiments of Allison upon learning of his Nobel honors. “I never expected my research, working on the immune system, would lead to the cancer therapy,” Honjo said in remarks to reporters following the Nobel announcement. “I’m very pleased to hear what I have done is really meaningful.” He described his “immense joy” at hearing from people who have credited his work for their recovery from serious illness. “When you hear things like that, there is no greater happiness.... On top of that, I am receiving such an award [as the Nobel Prize]. I really feel I am a fortunate person.”

Tasuku Honjo has been an Honorary Member of AAI (an honorific membership category for distinguished non-US scientists) since 1988. He is a Distinguished Professor Emeritus at Kyoto University, and a Distinguished Professor and Deputy Director General at the Kyoto University Institute for Advanced Study (KUIAS). Dr. Honjo is also the President of the Foundation for Biomedical Research and Innovation at Kobe. In addition to his three decades of AAI membership, he was chosen as a Distinguished Lecturer at the AAI annual meeting in 2000. Dr. Honjo is being honored for his work on PD-1, another inhibitory T cell molecule. Using an antibody to block the inhibitory pathway, he and his colleagues described its function and showed that by using a blocking antibody, tumor growth could be halted.

Allison and Honjo are recognized internationally for not only adding to our understanding of the basic mechanisms underlying immunotherapy, but also for their work on unique T cell subsets, TCR-MHC recognition, and the functional diversification of antibodies. Both men’s seminal works have been, or will be, featured in “Pillars” articles in The Journal of Immunology (A 2011 commentary discussing the observations that CTLA-4 inhibited T cell activation.) The Journal of Immunology will be featuring a publication by Tasuku Honjo investigating the role of activation-induced cytidine deaminase in class switch recombination and somatic hypermutation of B cells in an upcoming Pillars of Immunology commentary (November 1, 2018, pending).

AAI President JoAnne Flynn stated, “I extend my heartfelt congratulations to James Allison and Tasuku Honjo on being awarded the Nobel Prize in Physiology or Medicine for 2018. Their basic and translational research on immune system regulation led to breakthrough therapies now in use against cancer. Dr. Allison has dedicated a significant part of his career to translating his basic science into immunotherapies, and Dr. Honjo’s research identified other immune regulators that are targeted in treating cancer. These breakthroughs are a result of their passion for research, incredible perseverance, and creative minds. This is an amazing demonstration of the importance and power of basic immunology research.”

Dr. Allison was interviewed as part of the AAI Oral History Project. That interview can be viewed here.

Relevant Publications:

• Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992). Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J., 11(11), 3887–3895.
• Krummel, M.F., and Allison, J. P. (1995). CD28 and CTLA-4 Have Opposing Effects on the Response of T cells to Stimulation. J Exp Med, 182, 459-465.
• Leach, D. R., Krummel, M. F., & Allison, J. P. (1996). Enhancement of antitumor immunity by CTLA-4 blockade. Science, 271(5256), 1734–1736.
• Kwon, E. D., Hurwitz, A. A., Foster, B. A., Madias, C., Feldhaus, A. L., Greenberg, N. M., Burg, M.B. & Allison, J.P. (1997). Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci USA, 94(15), 8099–8103.
• Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999). Development of Lupus-like Autoimmune Diseases by Disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity, 11, 141–151.
• Freeman, G.J., Long, A.J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L.J., Malenkovich, N., Okazaki, T., Byrne, M.C., Horton, H.F., Fouser, L., Carter, L., Ling, V., Bowman, M.R., Carreno, B.M., Collins, M., Wood, C.R. & Honjo, T. (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med, 192(7), 1027–1034.
• Hodi, F.S., Mihm, M.C., Soiffer, R.J., Haluska, F.G., Butler, M., Seiden, M.V., Davis, T., Henry-Spires, R., MacRae, S., Willman, A., Padera, R., Jaklitsch, M.T., Shankar, S., Chen, T.C., Korman, A., Allison, J.P. & Dranoff, G. (2003). Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA, 100(8), 4712-4717.
• Iwai, Y., Terawaki, S., & Honjo, T. (2005). PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol, 17(2), 133–144.

(Posted October 2018)