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Thymic stromal lymphopoietin plays an adjuvant role in BCG-mediated CD8 cytotoxic T cell responses through dendritic cell activation
Authors:Hiroyuki Sugimoto  Tomoki ItoYoshitaro Torii  Hideki AmuroTakashi Yokoi  Tsutomu TanijiriRie Miyamoto  Naoko MurakamiRyuichi Amakawa  Shirou Fukuhara
Affiliation:First Department of Internal Medicine, Kansai Medical University, Osaka, 570-8506, Japan
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-γ without strong cell expansion, TSLP-stimulated DCs induced robust CD8+ T cell expansion without high quantities of IFN-γ production. Notably, DCs stimulated with both BCG and TSLP induced robust expansion of CD8+ T cells that produced a large amount of IFN-γ 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.
Keywords:TSLP   BCG   CD8+ T cell   Dendritic cell
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