title: CD40 immunotherapy for pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive and lethal cancer which is poorly responsive to standard therapies. Although the PDA tumor microenvironment is considered especially immunosuppressive, recent data mostly from genetically engineered and other mouse models of the disease suggest that novel immunotherapeutic approaches hold promise. Here, we describe both laboratory and clinical efforts to target the CD40 pathway for immunotherapy in PDA. Findings suggest that CD40 agonists can mediate both T-cell-dependent and T-cell-independent immune mechanisms of tumor regression in mice and patients. T-cell-independent mechanisms are associated with macrophage activation and the destruction of PDA tumor stroma, supporting the concept that immune modulation of the tumor microenvironment represents a useful approach in cancer immunotherapy.
authors.affiliation: Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5156, USA. rhv@exchange.upenn.edu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Vonderheide
authors.forename: David L
authors.initials: DL
authors.lastname: Bajor
authors.forename: Rafael
authors.initials: R
authors.lastname: Winograd
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Evans
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Bayne
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Beatty
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D019013:CD40 Antigens / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D059016:Tumor Microenvironment
chemical_list: D000906:Antibodies; D019013:CD40 Antigens; D007166:Immunosuppressive Agents