Thymic stromal lymphopoietin plays an adjuvant role in BCG-mediated CD8(+) cytotoxic T cell responses through dendritic cell activation.
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.
Sugimoto
Hiroyuki
H
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Ito
Tomoki
T
Torii
Yoshitaro
Y
Amuro
Hideki
H
Yokoi
Takashi
T
Tanijiri
Tsutomu
T
Miyamoto
Rie
R
Murakami
Naoko
N
Amakawa
Ryuichi
R
Fukuhara
Shirou
S
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
D000276:Adjuvants, Immunologic; C498762:CRLF2 protein, human; D016207:Cytokines; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D023201:CD40 Ligand; D000094632:Thymic Stromal Lymphopoietin