AI Article Synopsis

  • Cancer immunity relies on the activation of CD8 cytotoxic T lymphocytes (CTLs) through tumor-specific antigens presented on class I MHC molecules by dendritic cells (DCs).
  • Immunosuppressive DCs with fewer co-stimulatory signals may hinder CTL activation, while certain compounds like α-galactosylceramide (α-GalCer) can enhance the immune response by activating iNKT cells and changing tolerogenic DCs into immunogenic ones.
  • Sequential administration of α-GalCer can improve the effectiveness of DCs, leading to better CTL activation and tumor control, highlighting a potential strategy for cancer immunotherapy.

Article Abstract

Cancer immunity is mediated through the effective priming and activation of tumour-specific class I MHC molecule-restricted CD8 cytotoxic T lymphocytes (CTLs). DEC-205 dendritic cells (DCs) 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 CD8 CTLs. Immunosuppressive tolerogenic DCs 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 C57BL/6 (B6) mice and do not prime CD8 CTLs. In this study, we show that the growth of ongoing tumours was suppressed by activated CD8 CTLs 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 DCs. Moreover, we demonstrated that sequential repetitive intraperitoneal inoculation with α-GalCer every 48 hr appeared to convert tolerogenic DEC-205 DCs into immunogenic DCs with a higher expression of co-stimulatory molecules and a stronger cross-presentation capacity, which primed CTL precursors and induced tumour-specific CD8 CTLs within the tumour environment without activating iNKT cells. These findings provide a new basis for cancer immunotherapy to convert tolerogenic DEC-205 DCs within tumours into immunogenic DCs through the sequential administration of an immuno-potent lipid/glycolipid, and then activated immunogenic DCs with sufficient expression of co-stimulatory molecules prime and activate tumour-specific CD8 CTLs within the tumour to control tumour growth.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461099PMC
http://dx.doi.org/10.1111/imm.12733DOI Listing

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