title: Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+CD18+ cells and CD8+CD103+ cells by multi-epitope imaging.
abstract: Pancreatic cancer is characterized by an increasing incidence and an extremely poor prognosis. It is resistant to most of the conventional treatment modalities. Histomorphologically, it presents with a strong desmoplastic reaction around cancer cells, and lymphocytes are typically localized as aggregates in the fibrotic interstitial tissue. Using the method of multi-epitope imaging with fluorochrome-tagged specific MoAbs which allows the simultaneous localization and characterization of T cells in tissues, we studied phenotypes and distribution of tumour-infiltrating lymphocytes (TIL) in pancreatic cancer. CD3+ T cells comprised up to 90% of the tumour-infiltrating cells which were either CD4+ or CD8+, most of them being memory cells (CD45RO+). In decreasing order of frequency, T lymphocytes carried the markers for CD45RO, CD18, CD103 and TCR gammadelta. Very few natural killer cells (CD56+) were observed. Twenty percent of CD8+ were labelled with CD103. These CD8+CD103+ T cells, analogous to the gut intraepithelial lymphocytes (IEL), were found in the fibrous interstitial tissue. Furthermore, an inverse correlation was found between the expression of CD18, the beta2-integrin, which mediates adhesion of activated lymphocytes, and CD45RO in the CD8+ subset of TIL (P = 0.046). In conclusion, phenotyping of T lymphocytes in pancreatic cancer raises the possibility that pancreatic cancer cells develop several strategies to escape the T cell-induced cytolysis by (i) the aggregation of cytotoxic CD8+CD103+ T cells in the fibrous tissue distant from the tumour cells, and (ii) the presence of CD18-bearing cells which lack the expression of the activation marker CD45RO.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Ademmer
authors.forename: M
authors.initials: M
authors.lastname: Ebert
authors.forename: F
authors.initials: F
authors.lastname: Müller-Ostermeyer
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: M W
authors.initials: MW
authors.lastname: Büchler
authors.forename: W
authors.initials: W
authors.lastname: Schubert
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D039001:Integrin alpha Chains; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018821:CD18 Antigens; D016827:CD8 Antigens; D039001:Integrin alpha Chains; C091367:alpha E integrins