The Nobel Assembly announced in early October that it will bestow the 2011 Prize in Physiology or Medicine upon 3 renowned immunology researchers: Ralph M. Steinman, MD; Jules A. Hoffmann, PhD; and Bruce A. Beutler, MD.
“Their work had a profound impact on helping us understand how immune responses are generated,” says Louis M. Weiner, MD, director of the Georgetown Lombardi Comprehensive Cancer Center. “It revolutionized cancer immunology and immunology in general.”
In 1973, Steinman discovered a type of immune cell that he dubbed the dendritic cell. At the time, “the idea that these cells would be clinically useful wasn't on anyone's mind,” says Sarah Schlesinger, MD, an immunologist at Rockefeller University who worked with Steinman. But Steinman found that mature dendritic cells process and present antigens, allowing the immune system to decide whether an invader might be harmful. If so, the dendritic cells activate T cells, immune cells that help the body mount a defense.
But what, precisely, tripped the body's alarm system in the first place remained unclear until 1996, when Hoffmann discovered that fruit flies with mutated versions of the protein Toll died when infected with bacteria or fungi. Two years later, Beutler showed that mice with a mutation in an immune cell surface protein similar to Toll could survive infection with endotoxin, which usually kills mice and can cause septic shock in humans. As several more Toll-like receptors (TLR) were identified, scientists realized that triggering these TLRs spurred the innate immune response by promoting the maturation of antigen presenting cells.
In the last 15 years, an entire field has developed around these discoveries, says Pamela Ohashi, PhD, director of the Immune Therapy Program at the Ontario Cancer Institute, who studies T cells and tumor immunity. Researchers are attempting to exploit dendritic cells and TLR-induced maturation signals to amplify the body's response to cancer. The first cancer “vaccine” approved in the United States—sipuleucel-T (Provenge; Dendreon) for the treatment of advanced prostate cancer—may enhance dendritic cell function. Other cancer vaccines are under study. Clinical trials have also demonstrated the feasibility of TLR agonists, although none has garnered approval for treating cancer to date.
Steinman, a professor of immunology at Rockefeller University, died of pancreatic cancer just days before the October 3 award announcement. His survivors will receive half of the $1.5-million prize. Hoffman, a former director of the Institute for Molecular Cell Biology in Strasbourg, France, and Beutler, a researcher at the University of Texas Southwestern Medical Center in Dallas, will share the other half. Recipients will receive their prizes on December 10 in Stockholm.
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