title: Targeting tumor tolerance: A new hope for pancreatic cancer therapy?
abstract: With a 5-year survival rate of just 8%, pancreatic cancer (PC) is projected to be the second leading cause of cancer deaths by 2030. Most PC patients are not eligible for surgery with curative intent upon diagnosis, emphasizing a need for more effective therapies. However, PC is notoriously resistant to chemoradiation regimens. As an alternative, immune modulating strategies have recently achieved success in melanoma, prompting their application to other solid tumors. For such therapeutic approaches to succeed, a state of immunologic tolerance must be reversed in the tumor microenvironment and that has been especially challenging in PC. Nonetheless, knowledge of the PC immune microenvironment has advanced considerably over the past decade, yielding new insights and perspectives to guide multimodal therapies. In this review, we catalog the historical groundwork and discuss the evolution of the cancer immunology field to its present state with a specific focus on PC. Strategies currently employing immune modulation in PC are reviewed, specifically highlighting 66 clinical trials across the United States and Europe.
authors.affiliation: Department of Surgery, University of Florida, Gainesville, FL, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Delitto
authors.affiliation: Department of Oral Biology, University of Florida, Gainesville, FL, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallet
authors.affiliation: Department of Surgery, University of Florida, Gainesville, FL, USA. Electronic address: steven.hughes@surgery.ufl.edu.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hughes
mesh_terms: D000465:Algorithms; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000276:immunology; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D055261:Immunogenetic Phenomena / Q000502:physiology; D007167:Immunotherapy / Q000379:methods*; D008264:Macrophages / Q000276:immunology; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D017154:Stromal Cells / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D019496:Cancer Vaccines
keywords: Cancer immunology; Immune modulation; Immunotherapy; Innate immunity; Pancreatic cancer; Tumor-associated stroma