Paclitaxel-exposed ovarian cancer cells induce cancer‑specific CD4+ T cells after doxorubicin exposure through regulation of MyD88 expression

  • Authors:
    • Jee-Eun Kim
    • Min Ja Jang
    • Dong-Hoon Jin
    • Yoon Hee Chung
    • Byung-Sun Choi
    • Ga Bin Park
    • Yeong Seok Kim
    • Seonghan Kim
    • Dae Young Hur
    • Chien-Fu Hung
    • Daejin Kim
  • View Affiliations

  • Published online on: February 21, 2014     https://doi.org/10.3892/ijo.2014.2308
  • Pages: 1716-1726
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Abstract

Ovarian cancer has the highest mortality rate among gynecological malignancies due to high chemoresistance to the combination of platinum with taxane. Immunotherapy against ovarian cancer is a promising strategy to develop from animal-based cancer research. We investigated changes in the immunogenicity of paclitaxel-exposed ovarian cancer cells following exposure to other chemotherapeutic drugs. Murine ovarian surface epithelial cells (MOSECs) showed some resistance to paclitaxel, a first-line therapy for ovarian cancer. However, MOSECs pre-exposed to paclitaxel died through apoptosis after incubation with doxorubicin or cisplatin for 2 h. Injected into mice, the paclitaxel-exposed MOSECs post-treated with doxorubicin induced more MOSEC-specific CD4+ T cells and extended survival for a greater time than MOSECs treated with paclitaxel alone; and bone marrow-derived dendritic cells (BMDCs) expressed higher levels of co-stimulatory molecules and produced IL-12 after co-culture with paclitaxel-exposed MOSECs treated with doxorubicin. We also observed that in paclitaxel-exposed MOSECs treated with doxorubicin, but not cisplatin, the expression of MyD88 and related target proteins decreased compared to paclitaxel-exposed MOSECs only, while in BMDCs co-cultured with these MOSECs the expression of myeloid differentiation primary response gene 88 (MyD88) increased. These findings suggest that paclitaxel pre-exposed cancer cells treated with doxorubicin can induce significant apoptosis and a therapeutic antitumor immune response in advanced ovarian cancer.
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May-2014
Volume 44 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kim J, Jang MJ, Jin D, Chung YH, Choi B, Park GB, Kim YS, Kim S, Hur DY, Hung C, Hung C, et al: Paclitaxel-exposed ovarian cancer cells induce cancer‑specific CD4+ T cells after doxorubicin exposure through regulation of MyD88 expression. Int J Oncol 44: 1716-1726, 2014
APA
Kim, J., Jang, M.J., Jin, D., Chung, Y.H., Choi, B., Park, G.B. ... Kim, D. (2014). Paclitaxel-exposed ovarian cancer cells induce cancer‑specific CD4+ T cells after doxorubicin exposure through regulation of MyD88 expression. International Journal of Oncology, 44, 1716-1726. https://doi.org/10.3892/ijo.2014.2308
MLA
Kim, J., Jang, M. J., Jin, D., Chung, Y. H., Choi, B., Park, G. B., Kim, Y. S., Kim, S., Hur, D. Y., Hung, C., Kim, D."Paclitaxel-exposed ovarian cancer cells induce cancer‑specific CD4+ T cells after doxorubicin exposure through regulation of MyD88 expression". International Journal of Oncology 44.5 (2014): 1716-1726.
Chicago
Kim, J., Jang, M. J., Jin, D., Chung, Y. H., Choi, B., Park, G. B., Kim, Y. S., Kim, S., Hur, D. Y., Hung, C., Kim, D."Paclitaxel-exposed ovarian cancer cells induce cancer‑specific CD4+ T cells after doxorubicin exposure through regulation of MyD88 expression". International Journal of Oncology 44, no. 5 (2014): 1716-1726. https://doi.org/10.3892/ijo.2014.2308