Paclitaxel-exposed ovarian cancer cells induce cancerspecific CD4+ T cells after doxorubicin exposure through regulation of MyD88 expression
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.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
Document Type: Research Article
Department of Anatomy, Chung-Ang University, College of Medicine, Seoul, Republic of Korea
Institute for Innovate Cancer Research, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea
Department of Preventive Medicine, Chung-Ang University, College of Medicine, Seoul, Republic of Korea
Department of Anatomy, Inje University, College of Medicine, Busan, Republic of Korea
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
May 1, 2014
More about this publication?
The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
- Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Information for Advertisers
- Terms & Conditions
- Ingenta Connect is not responsible for the content or availability of external websites