title: Dendritic cell immunotherapy combined with gemcitabine chemotherapy enhances survival in a murine model of pancreatic carcinoma.
abstract: Pancreatic cancer is an extremely aggressive malignancy with a dismal prognosis. Cancer patients and tumor-bearing mice have multiple immunoregulatory subsets including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) that may limit the effectiveness of anti-tumor immunotherapies for pancreatic cancer. It is possible that modulating these subsets will enhance anti-tumor immunity. The goal of this study was to explore depletion of immunoregulatory cells to enhance dendritic cell (DC)-based cancer immunotherapy in a murine model of pancreatic cancer. Flow cytometry results showed an increase in both Tregs and MDSC in untreated pancreatic cancer-bearing mice compared with control. Elimination of Tregs alone or in combination with DC-based vaccination had no effect on pancreatic tumor growth or survival. Gemcitabine (Gem) is a chemotherapeutic drug routinely used for the treatment for pancreatic cancer patients. Treatment with Gem led to a significant decrease in MDSC percentages in the spleens of tumor-bearing mice, but did not enhance overall survival. However, combination therapy with DC vaccination followed by Gem treatment led to a significant delay in tumor growth and improved survival in pancreatic cancer-bearing mice. Increased MDSC were measured in the peripheral blood of patients with pancreatic cancer. Treatment with Gem also led to a decrease of this population in pancreatic cancer patients, suggesting that combination therapy with DC-based cancer vaccination and Gem may lead to improved treatments for patients with pancreatic cancer.
authors.affiliation: Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Tomar
authors.initials: T
authors.lastname: Ghansah
authors.forename: Nasreen
authors.initials: N
authors.lastname: Vohra
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kinney
authors.forename: Amy
authors.initials: A
authors.lastname: Weber
authors.forename: Krithika
authors.initials: K
authors.lastname: Kodumudi
authors.forename: Gregory
authors.initials: G
authors.lastname: Springett
authors.forename: Amod A
authors.initials: AA
authors.lastname: Sarnaik
authors.forename: Shari
authors.initials: S
authors.lastname: Pilon-Thomas
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002277:Carcinoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D051379:Mice; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine