title: Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation.
abstract: Keratinocyte growth factor (KGF), which is given exogenously to allogeneic bone marrow transplantation (allo-BMT) recipients, supports thymic epithelial cells and increases thymic output of naive T cells. Here, we demonstrate that this improved T-cell reconstitution leads to enhanced responses to DNA plasmid tumor vaccination. Tumor-bearing mice treated with KGF and DNA vaccination have improved long-term survival and decreased tumor burden after allo-BMT. When assayed before vaccination, KGF-treated allo-BMT recipients have increased numbers of peripheral T cells, including CD8(+) T cells with vaccine-recognition potential. In response to vaccination, KGF-treated allo-BMT recipients, compared with control subjects, generate increased numbers of tumor-specific CD8(+) cells, as well as increased numbers of CD8(+) cells producing interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). We also found unanticipated benefits to antitumor immunity with the administration of KGF. KGF-treated allo-BMT recipients have an improved ratio of T effector cells to regulatory T cells, a larger fraction of effector cells that display a central memory phenotype, and effector cells that are derived from a broader T-cell-receptor repertoire. In conclusion, our data suggest that KGF can function as a potent vaccine adjuvant after allo-BMT through its effects on posttransplantation T-cell reconstitution.
authors.affiliation: Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jenq
authors.forename: Christopher G
authors.initials: CG
authors.lastname: King
authors.forename: Christine
authors.initials: C
authors.lastname: Volk
authors.forename: David
authors.initials: D
authors.lastname: Suh
authors.forename: Odette M
authors.initials: OM
authors.lastname: Smith
authors.forename: Uttam K
authors.initials: UK
authors.lastname: Rao
authors.forename: Nury L
authors.initials: NL
authors.lastname: Yim
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Holland
authors.forename: Sydney X
authors.initials: SX
authors.lastname: Lu
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Zakrzewski
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Goldberg
authors.forename: Adi
authors.initials: A
authors.lastname: Diab
authors.forename: Onder
authors.initials: O
authors.lastname: Alpdogan
authors.forename: Olaf
authors.initials: O
authors.lastname: Penack
authors.forename: Il-Kang
authors.initials: IK
authors.lastname: Na
authors.forename: Lucy W
authors.initials: LW
authors.lastname: Kappel
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: Alan N
authors.initials: AN
authors.lastname: Houghton
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods / Q000401:mortality; D015704:CD4 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D019496:Cancer Vaccines / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D019496:Cancer Vaccines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D019444:Vaccines, DNA; D051523:Fibroblast Growth Factor 7