title: Monitoring and functional characterization of the lymphocytic compartment in pancreatic ductal adenocarcinoma patients.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDAC) still has a poor prognosis and current treatments including immunotherapy often fail. This might be due to the pronounced immunosuppressive milieu impairing infiltration and function of immune effector cells. This study aimed at a comprehensive analysis of immune cells in PDAC patients by determining absolute and relative peripheral blood cell numbers of immune cell subsets along with their functional capacity.
  
  
  METHODS
  Whole blood cells or isolated peripheral blood mononuclear cells were characterized by flow cytometry. PDAC tissues were analyzed by immunohistochemistry. Anti-tumor activity of immune effector cells was determined by RTCA system.
  
  
  RESULTS
  Our data demonstrate that relative CD4+memory- and regulatory T cell numbers were enhanced, whereas determination of absolute cell numbers revealed generally lower immune cell numbers in PDAC patients compared to healthy controls. γδ T cells accumulated at higher numbers compared to αβ T cells in the malignant ductal epithelium of PDAC tissues indicating that γδ T cells infiltrate into the tumor. Cytotoxicity against tumor cells of even small numbers of T- and NK cells could be induced by a bispecific antibody targeting CD3+T cells to human epidermal growth factor receptor (HER)2 expressing PDAC cells or Trastuzumab. Importantly, a critical number of γδ T cells was required for significant tumor cell killing by a bispecific antibody engaging the γδ T cell receptor on γδ T cells and HER2 on tumor cells.
  
  
  CONCLUSIONS
  Monitoring immune cells along with the determination of their functional capacity provides a comprehensive assessment as a prerequisite for a personalized immunotherapeutic PDAC treatment.
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Oberg
authors.affiliation: Medical Department I, Laboratory of Experimental Oncology, UKSH Campus Lübeck, Lübeck, Germany.
authors.forename: Evelin
authors.initials: E
authors.lastname: Grage-Griebenow
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Adam-Klages
authors.affiliation: Institute for Experimental Cancer Research, Group Inflammatory Carcinogenesis, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Elfi
authors.initials: E
authors.lastname: Jerg
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peipp
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kellner
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Domantas
authors.initials: D
authors.lastname: Petrick
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonnermann
authors.affiliation: Institute for Medical Informatics and Statistics, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Freitag-Wolf
authors.affiliation: Department of Pathology, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.affiliation: Medical Department III, Community Hospital Kiel, Kiel, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Sebens
authors.affiliation: Department of Surgery, Community Hospital Kiel, Kiel, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Vogel
authors.affiliation: Department of General and Thoracic Surgery, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.affiliation: Institute of Pathology, Community Hospital Kiel, Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ebsen
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Wesch
authors.affiliation: Institute for Experimental Cancer Research, Group Inflammatory Carcinogenesis, Christian-Albrechts-University Kiel, Kiel, Germany. Electronic address: susanne.sebens@email.uni-kiel.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Sebens
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Immune escape; Immune status; Immune therapy; Pancreatic cancer; γδ T cells