title: Soluble fibrin inhibits lymphocyte adherence and cytotoxicity against tumor cells: implications for cancer metastasis and immunotherapy.
abstract: Circulating soluble fibrin (sFn) is elevated in many cancer patients. It is a marker for ongoing disseminated intravascular coagulation and may have prognostic significance. We have demonstrated that sFn inhibited monocyte adherence and cytotoxicity by a mechanism involving blockade of monocyte alphaMbeta2 and tumor cell CD54. It was, therefore, hypothesized that sFn also inhibits lymphocyte and interleukin-2-activated lymphocyte (LAK) adherence and cytotoxicity against tumor cells. This study sought to identify the lymphocyte subset responsible for adherence and killing of A375 melanoma cells and whether sFn inhibited these parameters. Lymphocyte and LAK cell adherence and cytotoxicity, which was adherence dependent, were inhibited by preincubation with purified or plasma-derived sFn. The lymphocyte and LAK cell activities were primarily a result of CD8(+) MHC (major histocompatibility complex) unrestricted cytotoxic T cells. These results suggest that elevated levels of circulating sFn may be immunosuppressive and may reduce the efficacy of adoptive immunotherapies.
authors.affiliation: Biological Imaging Unit, University of Tennessee, Knoxville, TN 37996, USA. jbiggers@utk.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Biggerstaff
authors.forename: Brandy
authors.initials: B
authors.lastname: Weidow
authors.forename: Judith
authors.initials: J
authors.lastname: Dexheimer
authors.forename: Gary
authors.initials: G
authors.lastname: Warnes
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vidosh
authors.forename: Shonak
authors.initials: S
authors.lastname: Patel
authors.forename: Michael
authors.initials: M
authors.lastname: Newman
authors.forename: Pretesh
authors.initials: P
authors.lastname: Patel
mesh_terms: D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005337:Fibrin / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000276:immunology*
chemical_list: D005337:Fibrin