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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1716-1726
Number of pages11
JournalInternational journal of oncology
Volume44
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • CD4
  • Doxorubicin
  • MyD88
  • Ovarian cancer
  • Paclitaxel

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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