Epothilone B enhances Class i HLA and HLA-A2 surface molecule expression in ovarian cancer cells

Ilenia Pellicciotta, Chia Ping Huang Yang, Gary L. Goldberg, Shohreh Shahabi

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)625-631
Number of pages7
JournalGynecologic Oncology
Volume122
Issue number3
DOIs
StatePublished - Sep 1 2011

Keywords

  • Epothilone B
  • HLA Class I
  • Hey cells
  • Ovarian cancer
  • Taxol
  • Vinblastine

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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