Dr. George Miller from New York University School of Medicine is the recipient of the $50,000 Ruth Leff Siegel Award. He was recognized for 2 recent seminal papers which elucidate our understanding of immune-suppression in pancreatic carcinoma and can have impact on the potential immunotherapy of this disease. His paper entitled “γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation” (Cell, 2016) identified a distinct γδT cell population, which constituted up to 70% of all tumor-infiltrating T cells in human pancreatic cancer. His research highlighted that specific γδT cell populations are key suppressors of effector T cell activation in tumors via reciprocal cross-talk. This study lays the framework for targeting γδT cells as a novel immunotherapy strategy for pancreatic cancer. His other paper entitled “The Necrosome Promotes Pancreas Oncogenesis via CXCL1 and Mincle Induced Immune Suppression” (Nature, 2016) investigated the significance of necroptosis, or programmed necrosis, in pancreas cancer. Dr. Miller’s group showed that pancreatic cancer cells – which were widely believed to die via apoptosis – also die via necroptosis which is dependent on RIP1 and RIP3 co-association. They showed that chemotherapy can further induce cancer cell death by necroptosis. However, despite its primary effect in facilitating cancer cell death, Dr. Miller discovered that necroptosis paradoxically promotes pancreatic oncogenesis via its secondary effects in driving immune-suppressive inflammation. His mechanistic work elucidated parallel networks of necroptosis-induced CXCL1 and Mincle signaling which promote myeloid cell-entrained suppression of T cell immunity which enabled pancreatic cancer progression. The scientific import of this discovery is high as the necrosome and Mincle had not previously been linked to oncogenesis. Moreover, this work identifies multiple potential targets for immunotherapy (RIP1, RIP3, CXCL1, Mincle) which can be tested in the clinic.
Dr. Miller is Associate Professor at NYU School of Medicine where he holds the H. Leon Pachter Chair in Surgery. He is Vice-Chairman for Research in the Surgery Department, leader of NYU’s Tumor Immunology Program, and Director of its T32 training program in GI Oncology. Dr. Miller is a physician-scientist in the real sense. From a clinical standpoint, he performs complex operations in patients with liver and pancreatic cancer. Nevertheless, 80% of his time is dedicated to basic and translational cancer immunology research. His lab has been a leader in illuminating immune-regulatory networks in the pancreatic cancer tumor microenvironment. Dr. Miller is PI on 4 current R01 grants, he has received a number of foundation awards, and he has trained a cadre of physician-investigators, all of whom have received prestigious training grants and are embarking on academic careers. A number of his findings in the lab are being translated into investigator-initiated clinical trials. He also recently founded a start-up company NYBO Therapeutics which is developing new immunotherapy drugs based on work in his lab. Dr. Miller has chaired federal grant study sections and is Editor-in-Chief of Oncogene.
The recipient of the $25,000 award is Dr. Susan Bates for her work as editor in chief of the dedicated pancreas Clinical Cancer Research journal titled “Pancreatic Cancer: Challenge and Inspiration” published in April 2017.
Dr. Bates received her M.D. degree from the University of Arkansas School of Medicine. She completed her clinical training in internal medicine at Georgetown University in Washington, D.C., and in medical oncology at the National Cancer Institute (NCI) in Bethesda, MD. Dr. Bates was a Lead Clinical Investigator and Head of the Molecular Therapeutics Section in the Developmental Therapeutics Branch of the Center for Cancer Research before moving to Columbia University in August 2015.
Dr. Bates' current interests are both laboratory and clinical in nature. Her laboratory efforts include laboratory and translational studies on drug resistance in T-cell lymphomas and advanced solid tumors including breast, pancreatic, neuroendocrine, renal and lung cancers. Her work is dedicated to new drug development, and finding antineoplastic agents that, alone or in combination with other anticancer agents, improve the options available for difficult to treat cancers. Emanating from the clinical and translational development of romidepsin, a histone deacetylase (HDAC) inhibitor, a current focus is on epigenetic therapies, and the development of combination therapies to use with HDAC inhibitors in refractory advanced cancers, including solid tumors. She also has a special interest in drug delivery and drug distribution and the role of the blood brain barrier in creating a sanctuary site for cancers that metastasize to the brain. Clinically, her goal has always been to translate ideas from the laboratory to clinical trials, an effort that has proven very successful. Clinically she seeks to develop combination therapies with histone deacetylase inhibitors for the therapy of solid tumors; and to develop therapies to treat central nervous system metastases, a complication of cancer that is becoming a greater problem as patients live longer with cancer.