TY - JOUR
T1 - Epothilone B enhances Class i HLA and HLA-A2 surface molecule expression in ovarian cancer cells
AU - Pellicciotta, Ilenia
AU - Yang, Chia Ping Huang
AU - Goldberg, Gary L.
AU - Shahabi, Shohreh
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
KW - Epothilone B
KW - HLA Class I
KW - Hey cells
KW - Ovarian cancer
KW - Taxol
KW - Vinblastine
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UR - http://www.scopus.com/inward/citedby.url?scp=80955179580&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2011.05.007
DO - 10.1016/j.ygyno.2011.05.007
M3 - Article
C2 - 21621254
AN - SCOPUS:80955179580
SN - 0090-8258
VL - 122
SP - 625
EP - 631
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -