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Tumor-infiltrating effector cells of ?-galactosylceramide-induced antitumor immunity in metastatic liver tumor

Takuya Osada; Hirokazu Nagawa; Yoichi Shibata

Journal of Immune Based Therapies and Vaccines 2(1): 7-0

2004

ISSN/ISBN: 1476-8518
DOI: 10.1186/1476-8518-2-7
Accession: 036423918
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?-Galactosylceramide (?-GalCer) can be presented by CD1d molecules of antigen-presenting cells, and is known to induce a potent NKT cell-dependent cytotoxic response against tumor cells. However, the main effector cells in ?-GalCer-induced antitumor immunity are still controversial. Methods In order to elucidate the cell phenotype that plays the most important role in ?-GalCer-induced antitumor immunity, we purified and analyzed tumor-infiltrating leukocytes (TILs) from liver metastatic nodules of a colon cancer cell line (Colon26), comparing ?-GalCer- and control vehicle-treated mice. Flow cytometry was performed to analyze cell phenotype in TILs and IFN-? ELISA was performed to detect antigen-specific immune response. Results Flow cytometry analysis showed a significantly higher infiltration of NK cells (DX5+, T cell receptor ?? (TCR)-) into tumors in ?-GalCer-treated mice compared to vehicle-treated mice. The DX5+TCR+ cell population was not significantly different between these two groups, indicating that these cells were not the main effector cells. Interestingly, the CD8+ T cell population was increased in TILs of ?-GalCer-treated mice, and the activation level of these cells based on CD69 expression was higher than that in vehicle-treated mice. Moreover, the number of tumor-infiltrating dendritic cells (DCs) was increased in ?-GalCer-treated mice. IFN-? ELISA showed stronger antigen-specific response in TILs from ?-GalCer-treated mice compared to those from vehicle-treated mice, although the difference between these two groups was not significant. Conclusions In ?-GalCer-induced antitumor immunity, NK cells seem to be some of the main effector cells and both CD8+ T cells and DCs, which are related to acquired immunity, might also play important roles in this antitumor immune response. These results suggest that ?-GalCer has a multifunctional role in modulation of the immune response.

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