title: Epothilone B enhances Class I HLA and HLA-A2 surface molecule expression in ovarian cancer cells.
abstract: OBJECTIVE
  Ovarian cancer is the leading cause of death from gynecologic cancers in the United States. Epothilone B (EpoB), Taxol and vinblastine are anti-neoplastic agents that interfere with microtubules and arrest the cell cycle in the G2/M phase. EpoB is being evaluated in phase III clinical trials, and its analogs are currently being used in the treatment of taxane-resistant metastatic breast cancer. Little is known about the effect of these drugs on the immune response to tumors. Cancer cells evade immune recognition by down-regulating HLA Class I expression, allowing escape from immune surveillance and destruction. Our data illustrates the effect of microtubule-interacting agents on HLA Class I and HLA-A2 expression as well as the modulation of cytokine expression in ovarian cancer cells.
  
  
  METHODS
  Ovarian cancer cells were treated with different concentrations of drugs. Cell surface expression and mRNA transcription of HLA Class I molecules and HLA-A2 was examined. IFNα, IL1β, IL12 and IL6 mRNA expression was also evaluated upon EpoB treatment.
  
  
  RESULTS
  Low-dose EpoB, Taxol and vinblastine greatly increased expression of HLA Class I and HLA-A2 molecules in Hey ovarian cancer cells. EpoB does not modulate HLA expression in drug-resistant ovarian cancer cells. The expression of IFNα, IL1β, IL12 and IL6 is also markedly increased upon EpoB treatment.
  
  
  CONCLUSIONS
  Nanomolar concentrations of microtubule-interacting agents enhance immune-visibility of ovarian cancer cells by increasing HLA Class I and pro-inflammatory cytokine expression. Immune recognition of tumor cells may be improved.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology and Women's Health, Montefiore Medical Center, the Albert Einstein College of Medicine and the Albert Einstein Cancer Center, Bronx, New York, NY 10461, USA. ileniap@hotmail.com
authors.forename: Ilenia
authors.initials: I
authors.lastname: Pellicciotta
authors.forename: Chia-Ping Huang
authors.initials: CP
authors.lastname: Yang
authors.forename: Gary L
authors.initials: GL
authors.lastname: Goldberg
authors.forename: Shohreh
authors.initials: S
authors.lastname: Shahabi
mesh_terms: D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D034261:Epothilones / Q000494:pharmacology*; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D050257:Tubulin Modulators / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D016207:Cytokines; D034261:Epothilones; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D012333:RNA, Messenger; D050257:Tubulin Modulators; D014747:Vinblastine; D017239:Paclitaxel; C093788:epothilone B