title: Characterization of immune responses in gastric cancer patients: a possible impact of H. pylori to polarize a tumor-specific type 1 response?
abstract: Recently, we were able to show that Helicobacter pylori-positive gastric cancer (GC) patients have a significantly better survival after the complete resection of their tumor compared to H. pylori-negative GC patients. H. pylori is known to polarize an immune response towards a type 1 cytokine profile and tumor-specific type 1 cytokine responses are associated with protection from tumor challenge and T-cell-mediated tumor regression. Therefore, we hypothesized that the improved survival in H. pylori-positive patients may be secondary to the induction of a GC-specific type 1 T cell response. To characterize the anti-tumor immune response in GC patients we analyzed tumor-infiltrating lymphocytes (TIL) isolated from primary tumors. The CD3+ T cell population contained 50% CD4+ (range 0.4-81%) and 39% CD8+ cells (range 22-53%). The number of B cells (CD19+, P = 0.03) was significantly increased and the number of T cells (CD3+, P = 0.02) significantly decreased in intestinal compared to diffuse type of tumors. Four tumor cell lines were established from primary GCs and three from lymph node metastases. T cell cultures were established from isolated TIL from four H. pylori-positive and one H. pylori-negative GC patients and tested for tumor-specific cytokine secretion. Eight of ten T cell cultures derived from H. pylori-positive patients secreted both IFN-gamma and IL-5 after restimulation with autologous tumor cells. The only tumor-specific TIL line expressing a dominant IL-5 response was derived from an H. pylori-negative patient.
authors.affiliation: Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany. Natasja.vandenEngel@med.uni-muenchen.de
authors.forename: Natasja K
authors.initials: NK
authors.lastname: van den Engel
authors.forename: Hauke
authors.initials: H
authors.lastname: Winter
authors.forename: Dominik
authors.initials: D
authors.lastname: Rüttinger
authors.forename: Irene
authors.initials: I
authors.lastname: Shau
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiller
authors.forename: Barbara
authors.initials: B
authors.lastname: Mayer
authors.forename: Tarsem
authors.initials: T
authors.lastname: Moudgil
authors.forename: Georgios
authors.initials: G
authors.lastname: Meimarakis
authors.forename: Manfred
authors.initials: M
authors.lastname: Stolte
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Fox
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Hatz
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000473:pathology / Q000821:virology; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology*