Costimulatory ligand CD70 allows induction of CD8+ T-cell immunity by immature dendritic cells in a vaccination setting.
The use of dendritic cells (DCs) as anticancer vaccines holds promise for therapy but requires optimization. We have explored the potential of costimulatory ligand CD70 to boost the capacity of DCs to evoke effective CD8(+) T-cell immunity. We show that immature conventional DCs, when endowed with CD70 expression by transgenesis, are converted from a tolerogenic state into an immunogenic state. Adoptively transferred CD70-expressing immature DCs could prime CD8(+) T cells, by CD27, to become tumor-eradicating cytolytic effectors and memory cells with a capacity for robust secondary expansion. The CD8(+) T-cell response, including memory programming, was independent of CD4(+) T-cell help, because the transferred immature DCs were loaded with major histocompatibility complex class I-restricted peptide only. Without CD70 expression, the DCs generated abortive clonal expansion, dysfunctional antitumor responses, and no CD8(+) T-cell memory. CD70-expressing CD8(+) DCs were the primary subset responsible for CD8(+) T-cell priming and performed comparably to fully matured DCs. These data highlight the importance of CD27/CD70 interactions at the T-cell/DC interface and indicate that CD70 should be considered in the design of DC vaccination strategies.
Keller
Anna M
AM
The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Xiao
Yanling
Y
Peperzak
Victor
V
Naik
Shalin H
SH
Borst
Jannie
J
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D053282:CD27 Ligand / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007111:Immunity, Cellular; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D053282:CD27 Ligand; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7