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Dr. Rafi Ahmed

Since 1975, the Cancer Research Institute (CRI) has bestowed the William B. Coley Award for Distinguished Research in Basic and Tumor Immunology on top scientists who have advanced our fundamental understanding of the complex relationship between cancer and the immune system, as well as our ability to translate that understanding into meaningful clinical breakthroughs. In September 2017, CRI honored Rafi Ahmed, PhD, with the William B. Coley Award in Basic Immunology and Thomas F. Gajewski, MD, PhD, with the William B. Coley Award in Tumor Immunology.

Dr. Ahmed is the director of the Emory Vaccine Center, a professor in the department of microbiology and immunology, and an investigator at the Emory Center for AIDS Research at Emory University (Atlanta, GA). Dr. Ahmed, also an Eminent Scholar of the Georgia Research Alliance, is being honored “for his seminal work on immune memory as well as his definitive studies of the role of the PD-1 receptor in T cell exhaustion during chronic infection.” Specifically, he contributed significantly to “our current understanding of memory T cell differentiation” and characterized the developmental program that CD8+ T cells, especially those distinguished by high expression of the IL7 receptor α-chain (IL7Rα), follow after initial antigen exposure and stimulation that ultimately leads to memory T-cell formation. Dr. Ahmed's investigations also uncovered the increased proliferative potential and persistence of central memory T cells (TCM) compared with effector memory T cells (TEM), and that, following antigen clearance, TEM are converted into TCM. This groundwork guided more recent efforts to improve the safety and efficacy of cell-based cancer immunotherapies, including chimeric antigen receptor T cells.

Dr. Ahmed's laboratory characterized the mechanisms responsible for T-cell “exhaustion” in the context of chronic viral infection and demonstrated that blocking the interaction between the PD-1 receptor and PD-L1 ligands can restore antiviral activity. When these mechanisms were also shown to be relevant to antitumor responses in cancer patients, they stimulated the clinical development of anti–PD-1/PD-L1 immunotherapies, five of which are now FDA approved. One of these became the first cancer treatment of any type to be approved for tumors characterized by a genetic marker, high microsatellite instability, or MSI-hi, regardless of their physical origin. Prior to receiving the Coley Award, Dr. Ahmed's work had been recognized through numerous awards, including the 2017 Robert Koch Award. He is also a member in the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Microbiology; a fellow of the American Association for the Advancement of Science; and member of the Indian National Academy of Sciences.

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Dr. Thomas Gajewski

Dr. Gajewski is the AbbVie Foundation Professor of Cancer Immunotherapy at the Ben May Department for Cancer Research, the leader of the immunology and cancer program, and a professor in the departments of pathology and medicine at the University of Chicago School of Medicine (Chicago, IL). In addition, he serves on several committees, for cancer biology, immunology, and molecular medicine, at the University of Chicago Comprehensive Cancer Center. Dr. Gajewski is being honored for his overall body of work, most especially his identification of a connection between the body's microbiome and antitumor immune responses, the antitumor effects of the STING pathway, and oncogenic pathways implicated in tumor immune escape. Dr. Gajewski's earliest breakthroughs showed how various cytokines, including IFNγ, dictate the proliferation and development of the contrasting Th1/Th2 T-cell subsets. Later, he built on these findings by investigating the ability of the Th1-promoting cytokine IL12 to promote antitumor immunity and translated this to vaccine trials in patients with melanoma. After demonstrating that downstream resistance mechanisms, including PD-L1/B7-H1 can diminish CD8+ T cell–mediated tumor rejection by blocking effector function, his subsequent work suggested that immunosuppressive tumor microenvironments, characterized by regulatory T cells and expression of IDO and PD-L1, developed only after T-cell infiltration and were “intrinsically driven by the immune system rather than being orchestrated by cancer cells,” providing an important rationale for using checkpoint immunotherapy to treat patients with “hot” tumors characterized by preexisting T-cell inflammation. More recently, Dr. Gajewski demonstrated that the activation of the DNA-sensing STING pathway is crucial for stimulating spontaneous antitumor immune responses, mediated in part through the innate immune system, as well as radiation-induced adaptive immune responses against tumors. This has propelled the development of clinical immunotherapy strategies taking advantage of this pathway. Looking for additional mechanisms that regulate the magnitude of endogenous antitumor immune responses, Dr. Gajewski identified a role for the commensal microbiota and found that Bifidobacterium could augment antimelanoma immune responses, both alone and in combination with anti–PD-1/PD-L1 immunotherapy. Dr. Gajewski has also defined the negative impact of tumor cell–intrinsic oncogene pathways on immune responses against cancer and identified the β-catenin signaling pathway that enabled tumors to prevent T-cell infiltration and, consequently, become more resistant to both anti–PD-1/PD-L1 and anti–CTLA-4 immunotherapies. Overall, Dr. Gajewski has greatly advanced our understanding of the interactions between tumors, immune cells, and other factors in tumor microenvironments and opened up new avenues of both laboratory investigation and translational clinical applications. Prior to receiving the Coley Award, Dr. Gajewski's work had been recognized through numerous awards, including the NCI of the NIH's 2017 Outstanding Investigator Award, and he was the recipient of the first American Cancer Society–Jules L. Plangere Jr. Family Foundation Professorship in Cancer Immunotherapy.

Arthur N. Brodsky

Cancer Research Institute, New York, NY