title: Thymic stromal lymphopoietin plays an adjuvant role in BCG-mediated CD8(+) cytotoxic T cell responses through dendritic cell activation.
abstract: Although Bacillus Calmette-Guérin (BCG) has historically emerged as a potent adjuvant in cancer immunization through dendritic cell (DC) activation, the efficacy of its antitumor effect has been limited. Therefore, the strategy of adjuvant therapy using BCG needs to be improved by adding enhancers. Here we found that thymic stromal lymphopoietin (TSLP) acts as an enhancer for the BCG-mediated antitumor effect. While BCG-stimulated DCs induced CD8(+) T cell production of IFN-gamma without strong cell expansion, TSLP-stimulated DCs induced robust CD8(+) T cell expansion without high quantities of IFN-gamma production. Notably, DCs stimulated with both BCG and TSLP induced robust expansion of CD8(+) T cells that produced a large amount of IFN-gamma with a potent cytolytic activity related to granzyme B expression. Our data suggest that TSLP is a good adjuvant to enhance the BCG-mediated cytotoxic T cell effect through DC activation, and provide a functional basis for a novel strategy for antitumor immune-based therapy.
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
authors.forename: Yoshitaro
authors.initials: Y
authors.lastname: Torii
authors.forename: Hideki
authors.initials: H
authors.lastname: Amuro
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tanijiri
authors.forename: Rie
authors.initials: R
authors.lastname: Miyamoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Murakami
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Amakawa
authors.forename: Shirou
authors.initials: S
authors.lastname: Fukuhara
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000328:Adult; D023201:CD40 Ligand / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D009163:Mycobacterium bovis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D018121:Receptors, Cytokine / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000502:physiology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000276:Adjuvants, Immunologic; C498762:CRLF2 protein, human; D016207:Cytokines; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D023201:CD40 Ligand; D000094632:Thymic Stromal Lymphopoietin