Abstract 2492: Microtubule-interacting agents increase Class I HLA and HLA-A2 molecules surface expression in ovarian cancer cells

Abstract

Abstract Objective: Ovarian cancer is the leading cause of death from gynecologic cancers in the United States. Standard first line therapy for ovarian cancer includes paclitaxel and platinum based agents. Epothilone B, Taxol and Vinblastin belong to a family of anti-neoplastic agents that interfere with microtubules and arrest cells in the G2/M phase of the cell cycle. Little is known about the effect of these drugs on the immune response to tumors. There is compelling evidence that cancer cells use multiple strategies to evade immune recognition. One of these mechanisms is the down-regulation of human leukocyte antigen (HLA) Class I molecule expression on the tumor cell surface, allowing the cancer cell to escape immune recognition and destruction. Data will be presented to illustrate the effect of microtubule affecting agents on HLA class I molecule expression in ovarian cancer cells. The effect on the expression of HLA-A2, the most common class I allele in the Caucasian population, has been evaluated as well. We also investigated the relationship between surface HLA expression and transcriptional modification of HLA induced by the drugs. Methods: IC50 was determined for each compound based on a 72 h cytotoxicity assay, using ovarian cancer cell line Hey. Cells were treated with different concentrations ranging from 1-fold IC50 to 100-fold IC50, and incubated at 37°C for 24 h, 48 h and 72 h. Cell surface expression of HLA class I molecules and HLA-A2 was examined by flow cytometry, using anti-HLA-A,B,C antibody (G46-2.6 clone) and HLA-A2 (BB7.2 clone). RT-PCR and real time PCR were used to amplify HLA genes, using Platinum Taq DNA Polymerase and Power SYBR Green master mix respectively. Results: Low dose Epothilone B, Taxol and Vinblastin (10-fold IC50) increased cell surface expression of HLA Class I up to four-fold in Hey ovarian cancer cells. HLA-A2 molecules were increased up to 2-fold. The increase of HLA Class I molecule expression was dose- and time-dependent. Conclusions: Nanomolar concentrations of microtubule-interacting agents increase the expression of HLA class I molecules in Hey ovarian cancer cells. Our data suggest that low doses of microtubule-interacting agents can mediate modulation of surface HLA expression and may enhance immune recognition of tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2492.