Pancreatic ductal adenocarcinoma (PDA) is resistant to most forms of therapy and is one of the most deadly types of cancer. The environment that surrounds cancer cells is referred to as the tumor microenvironment, and studies in mice and humans have shown that the PDA tumor microenvironment has unique characteristics that are thought to limit the efficacy of treatment. By understanding the obstacles that prevent the tumor from responding to treatments, it should be possible to develop therapeutic agents to eliminate these barriers resulting in the effective treatment of PDA.
T cell-based cancer immunotherapy has shown promise for the treatment of a variety of cancer types and was hailed as “Breakthrough of the Year” in 2013 by the journal Science. Despite its emerging promise, clinical efforts for immune therapy in PDA have lagged behind. Recent advances in PDA mouse models and in technologies to study cancer-associated immune processes at tumor sites have revealed that major anti-PDA immune responses can occur if antitumor T cell-generating approaches are combined with drugs that block immune suppression in the tumor. Based on promising initial clinical trials, this Dream Team’s goal is to “reprogram” the tumor microenvironment to fuel clinically meaningful anticancer immune responses in patients with PDA.
The Dream Team will use a “convergence” approach by bringing together leading individuals in the fields of immunotherapy, genetics, informatics, biostatistics, regulatory/clinical trials, cancer biology, and pathology. This group of experts will apply their efforts toward understanding and treating PDA.
The Dream Team will conduct combination clinical trials and establish biomarkers of tumor microenvironment reprogramming. Trials will focus on novel immune suppressive pathways within the tumor, either in combination with a T cell-activating vaccine or chemotherapy. These trials will also establish a national PDA biobank for identification of immune biomarkers. Preclinical studies in PDA mouse models will be conducted to establish novel multi-agent approaches and develop biomarkers that will drive the next generation of clinical trials.
Margaret A. Tempero, MD, University of California, San Francisco
Lisa M. Coussens, PhD, Oregon Health & Science University
David C. Linehan, MD, Washington University in St. Louis
Dafna Bar-Sagi, PhD, NYU Langone Medical Center
Irving L. Weissman, MD, Stanford University
Douglas T. Fearon, MD, University of Cambridge, United Kingdom
Steven D. Leach, MD, Memorial Sloan Kettering Cancer Center