Abstract
The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8+/IFN-γ+ tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer.
Highlights
Ovarian cancer accounts for only 3% of all malignancies in women, it is the most lethal gynecologic malignancy worldwide [1]
Intra-peritoneal Hyperthermia Enhanced the Secretion of Pro-inflammatory Cytokines Induced by a-GalCer
These results indicated that a-GalCer might induce stronger anti-tumor immune response mainly through the enhancement of Th1/Th2 cytokines expression by combining with i.p. hyperthermia
Summary
Ovarian cancer accounts for only 3% of all malignancies in women, it is the most lethal gynecologic malignancy worldwide [1]. Despite the increasing number of chemotherapeutic drugs available for recurrent disease, the course of ovarian cancer is usually characterized by repeated periods of remission and relapse, and in most cases the disease will eventually develop resistance to all chemotherapeutic agents and become incurable [5]. There are some drawbacks limiting its usage in treating the ovarian cancer, such as potential poor-healing of bowel anastomosis, risk of chemotherapeutic metabolites contamination to the surgical personnel through body fluid or inhalation of evaporating chemotherapy agents [11]. It cannot be applied repeatedly without exploration of the peritoneal cavity
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