title: Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors.
abstract: We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients.
  
  
  
  Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured.
  
  
  
  TIL expansion was measured in 19 patient samples. The majority of these TIL were CD4+T cells and were highly activated. Purified CD8+T cells produced IFN-γ in response to HLA-matched pancreatic tumor targets. PD-1 blockade and 4-1BB stimulation were demonstrated as effective strategies to improve effective TIL yield, including the production of tumor-reactive pancreatic TIL.
  
  
  
  TIL expanded from pancreatic tumors are functional and able to respond to pancreatic tumor associated antigens. PD-1 blockade, 41BB stimulation, and CD8+T cell enrichment are effective strategies to improve TIL yield and tumor reactivity. These results support the development of adoptive cell therapy strategies using TIL for the treatment of pancreatic cancer.
authors: Department of Immunology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors: MacLean
authors: M
authors: Hall
authors: Department of Immunology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors: Hao
authors: H
authors: Liu
authors: Gastrointestinal Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors: Mokenge
authors: M
authors: Malafa
authors: Gastrointestinal Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors: Barbara
authors: B
authors: Centeno
authors: Gastrointestinal Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors: Pamela J
authors: PJ
authors: Hodul
authors: Gastrointestinal Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.
authors: José
authors: J
authors: Pimiento
authors: Department of Immunology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.|Cutaneous Oncology Program, H Lee Moffitt Cancer Center and Research Institute, 10920 N. McKinley Dr, Tampa, FL 33612 USA.
authors: Shari
authors: S
authors: Pilon-Thomas
authors: Department of Immunology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.|Cutaneous Oncology Program, H Lee Moffitt Cancer Center and Research Institute, 10920 N. McKinley Dr, Tampa, FL 33612 USA.
authors: Amod A
authors: AA
authors: Sarnaik
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D018929:Cell Culture Techniques; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D000074322:Antineoplastic Agents, Immunological; D015415:Biomarkers; D006680:HLA Antigens; D007376:Interleukin-2; D061026:Programmed Cell Death 1 Receptor
keywords: Adoptive cell therapy; Pancreatic cancer; T cells; Tumor infiltrating lymphocytes (TIL)