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Suppression of murine tumour growth through CD 8 + cytotoxic T lymphocytes via activated DEC ‐205 + dendritic cells by sequential administration of α ‐galactosylceramide in vivo
Author(s) -
Kogo Hideki,
Shimizu Masumi,
Negishi Yasuyuki,
Uchida Eiji,
Takahashi Hidemi
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12733
Subject(s) - cytotoxic t cell , cd8 , ctl* , biology , priming (agriculture) , mhc class i , immunology , antigen , immunotherapy , major histocompatibility complex , epitope , cancer research , immune system , microbiology and biotechnology , in vitro , biochemistry , botany , germination
Summary Cancer immunity is mediated through the effective priming and activation of tumour‐specific class I MHC molecule‐restricted CD 8 + cytotoxic T lymphocytes ( CTL s). DEC ‐205 + dendritic cells ( DC s) can cross‐present the epitope(s) of captured tumour antigens associated with class I MHC molecules alongside co‐stimulatory molecules to prime and activate tumour‐specific CD 8 + CTL s. Immunosuppressive tolerogenic DC s with reduced co‐stimulatory molecules may be a cause of impaired CTL induction. Hepa1‐6‐1 cells were established from the mouse hepatoma cell line Hepa1‐6; these cells grow continuously after subcutaneous implantation into syngeneic C57 BL /6 (B6) mice and do not prime CD 8 + CTL s. In this study, we show that the growth of ongoing tumours was suppressed by activated CD 8 + CTL s with tumour‐specific cytotoxicity through the administration of the glycolipid α ‐galactosylceramide ( α ‐GalCer), which is a compound known to stimulate invariant natural killer T ( iNKT ) cells and selectively activate DEC ‐205 + DC s. Moreover, we demonstrated that sequential repetitive intraperitoneal inoculation with α ‐GalCer every 48 hr appeared to convert tolerogenic DEC ‐205 + DC s into immunogenic DC s with a higher expression of co‐stimulatory molecules and a stronger cross‐presentation capacity, which primed CTL precursors and induced tumour‐specific CD 8 + CTL s within the tumour environment without activating iNKT cells. These findings provide a new basis for cancer immunotherapy to convert tolerogenic DEC ‐205 + DC s within tumours into immunogenic DC s through the sequential administration of an immuno‐potent lipid/glycolipid, and then activated immunogenic DC s with sufficient expression of co‐stimulatory molecules prime and activate tumour‐specific CD 8 + CTL s within the tumour to control tumour growth.