title: T cell augments the antitumor activity of tumor-targeting Salmonella.
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.
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan. chlee@mail.cmu.edu.tw
authors.forename: Che-Hsin
authors.initials: CH
authors.lastname: Lee
authors.forename: Jeng-Long
authors.initials: JL
authors.lastname: Hsieh
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Wu
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Hsu
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Shiau
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use; D001691:Biological Therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000382:microbiology* / Q000628:therapy*; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D019779:Salmonella enterica / Q000276:immunology* / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents