title: Inducing anti-tumor cytokines and an immune response in melanoma by inhibition of MIA using the peptide AR71.
abstract: BACKGROUND
  Malignant melanoma is known for its aggressive metastatic spread and suppression of the host immune system. Immunosuppression in melanoma is mediated in part by the protein melanoma inhibitory activity (MIA).
  
  
  OBJECTIVE
  In this study, we assessed the in vitro and in vivo efficacy of the MIA-inhibitory peptide AR71 in the inhibition of MIA-induced immunosuppression. This follows a previous study that revealed an increase in CD3-positive cells and cleaved caspase-3 in an in vivo model of hepatic metastasis after MIA inhibition.
  
  
  METHODS
  We used Multiplex-ELISAs and qRT-PCR for determining changes in cytokine expression in vitro and in vivo and calcein release assays for determining immune cell response in vitro.
  
  
  RESULTS
  By evaluating the serum levels of tumor-associated cytokines of the melanoma-bearing mice, we found beneficial decreases of several cytokines, including TNF-alpha, after AR71 treatment. Additionally, we demonstrated an increase of anti-tumor lymphokine-activated killer (LAK) cell cytotoxicity in the presence of the MIA inhibitor AR71. Stimulation of anti-tumor immune responses by AR71 could be observed via increased numbers of NK cells in the metastases-bearing murine livers in vivo.
  
  
  CONCLUSIONS
  In summary, inhibition of MIA activity results in reduced immunosuppression in vitro and in vivo.
authors.affiliation: Institute of Pathology, University of Regensburg Franz-Josef-Strauss-Allee 11 D-93053 Regensburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Riechers
authors.affiliation: Fraunhofer Research Institution for Modular Solid State Technologies (EMFT), Regensburg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schmidt
authors.affiliation: Institute of Functional Genomics, University of Regensburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Dettmer
authors.affiliation: Institute of Functional Genomics, University of Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Oefner
authors.affiliation: Antisense Pharma GmbH, Regensburg, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Jachimczak
authors.affiliation: Antisense Pharma GmbH, Regensburg, Germany.
authors.forename: Anneliese
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Institute of Pathology, University of Regensburg Franz-Josef-Strauss-Allee 11 D-93053 Regensburg, Germany.
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors*; D007108:Immune Tolerance / Q000187:drug effects*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D019344:Lactic Acid / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D051379:Mice; D009842:Oligopeptides / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D016326:Extracellular Matrix Proteins; C513263:Mia protein, mouse; D009842:Oligopeptides; D012333:RNA, Messenger; C000595066:acetyl-phenylalanyl-histidyl-tryptophyl-arginyl-tyrosyl-prolyl-leucyl-prolyl-leucyl-prolyl-glycyl-glutaminamide; D019344:Lactic Acid
keywords: MIA; cytokine; immunosuppression; malignant melanoma; peptide inhibitor