enhancement of anti-tumor immunity in dendritic cell therapy toward gynecological malignancies

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Recent development in treatment modalities has achieved a marked improvement in the short-term survival of patients with ovarian cancer. Nevertheless, the long-term prognosis in advanced cases remains unsatisfactory, requiring a new paradigm in the treatment strategy. Various prognostic factors have been proposed and used clinically to predict the clinical course and to aid clinical decision-making in ovarian cancer patients. However, even using this system, prediction of the long-term prognosis, especially of late recurrence after remission remains difficult, suggesting a need to introduce other parameters such as sensitivity to chemotherapy and the strength of anti-tumor immune response. Several reports have shown the significance of tumor-infiltrating lymphocytes (TILs) as a prognostic factor in malignant tumors such as cutaneous melanoma, colorectal cancer, esophageal cancer, renal cancer, and ovarian cancer, suggesting that immunological parameters are significant and useful in as … More sessing the prognosis of cancer patients. However, there are few reports suggesting that a specific molecule can represent the strength of the host-tumor immunity. Therefore, in this project, we firstly analyzed if some of these immunological parameters are really related to the prognosis of the patient, and found that CD8+T cell number in the tumor as well as PD-L1 expression (ovarian cancer), or COX-2 expression (cervical adenocarcinoma) correlated with patient prognosis, indicating that tumor immunity is indeed important. Then, we tried to establish a method to acquire efficient tumor immunity toward ovarian cancer. Human dendiritic cells were collected from ovarian cancer patient blood with informed consent and anti-tumor immunity toward autologus ovarian cancer was measured in various conditions. Anti-tumor immunity was enhanced when DCs were co-cultured with K-562 cells transfected with and overexpressed Flt-3, suggesting that immunostimulatory signal from bystander cells can enhance tumor immunity. We are now preparing a mouse in vivo model of immunotherapy to deliver immunostimulatory signal using non-immune cell Less