T cell augments the antitumor activity of tumor-targeting <Emphasis Type="Italic">Salmonella</Emphasis> |
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Authors: | Che-Hsin Lee Jeng-Long Hsieh Chao-Liang Wu Pei-Yu Hsu Ai-Li Shiau |
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Institution: | (1) Department of Microbiology, School of Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan;(2) Department of Nursing, Chung Hwa University of Medical Technology, Tainan, Taiwan;(3) Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan;(4) China Medical University Hospital, Taichung, Taiwan;(5) Department of Microbiology and Immunology, National Cheng Kung University Medical College, 1 Dashiue Road, Tainan, 70101, Taiwan |
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Abstract: | Systemic administration of Salmonella to tumor-bearing mice leads to preferential accumulation within tumor sites and retardation of tumor growth. However, the
detailed mechanism of Salmonella-induced antitumor immune response via host T cell remains uncertain. Herein, we used wild-type, CD4+ T-cell-deficient, and CD8+ T-cell-deficient mice to study the role of T cell in the antitumor immune responses induced by Salmonella enterica serovar Choleraesuis (Salmonella Choleraesuis). When systemically administered into mice bearing tumors, Salmonella Choleraesuis significantly inhibited tumor growth by 50%. In contrast, in T-cell-deficient mice, there was only 34–42% inhibition
of tumor growth. We found that treatment with Salmonella Choleraesuis significantly upregulates interferon-γ in wild-type and CD8+ T-cell-deficient mice, but not in CD4+ T-cell-deficient mice. Furthermore, immunohistochemical staining of the tumors revealed more infiltration of macrophages
and neutrophils in wild-type mice after Salmonella Choleraesuis treatment compared with those in T-cell-deficient mice. The antitumor therapeutic effect mediated by Salmonella Choleraesuis is associated with an inflammatory immune response at the tumor site and a tumor T helper 1-type immune response.
In conclusion, these results suggest that tumor-targeted therapy using Salmonella Choleraesuis, which exerts tumoricidal effects and stimulates T cell activities, represents a potential strategy for the
treatment of tumor. |
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