Intra-peritoneal hyperthermia combining α-galactosylceramide in the treatment of ovarian cancer.
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.
Graduate Institute of Mechanical and Electrical Engineering, National Taipei University of Technology, Taipei City, Taiwan.
Chao-Chih
CC
Wu
Yin-Ting
YT
Chuang
Yun-Ting
YT
Hsu
Jung-Tang
JT
Huang
T-C
TC
Wu
Chien-Fu
CF
Hung
Yuh-Cheng
YC
Yang
Chih-Long
CL
Chang
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology / Q000627:therapeutic use*; D006979:Hyperthermia, Induced; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology*; D010587:Phagocytosis / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D005699:Galactosylceramides; D018836:Inflammation Mediators; C493154:alpha-galactosylceramide