title: Salmonella typhimurium Suppresses Tumor Growth via the Pro-Inflammatory Cytokine Interleukin-1β.
abstract: Although strains of attenuated Salmonella typhimurium and wild-type Escherichia coli show similar tumor-targeting capacities, only S. typhimurium significantly suppresses tumor growth in mice. The aim of the present study was to examine bacteria-mediated immune responses by conducting comparative analyses of the cytokine profiles and immune cell populations within tumor tissues colonized by E. coli or attenuated Salmonellae. CT26 tumor-bearing mice were treated with two different bacterial strains: S. typhimurium defective in ppGpp synthesis (ΔppGpp Salmonellae) or wild-type E. coli MG1655. Cytokine profiles and immune cell populations in tumor tissue colonized by these two bacterial strains were examined at two time points based on the pattern of tumor growth after ΔppGpp Salmonellae treatment: 1) when tumor growth was suppressed ('suppression stage') and 2) when they began to re-grow ('re-growing stage'). The levels of IL-1β and TNF-α were markedly increased in tumors colonized by ΔppGpp Salmonellae. This increase was associated with tumor regression; the levels of both IL-1β and TNF-α returned to normal level when the tumors started to re-grow. To identify the immune cells primarily responsible for Salmonellae-mediated tumor suppression, we examined the major cell types that produce IL-1β and TNF-α. We found that macrophages and dendritic cells were the main producers of TNF-α and IL-1β. Inhibiting IL-1β production in Salmonellae-treated mice restored tumor growth, whereas tumor growth was suppressed for longer by local administration of recombinant IL-1β or TNF-α in conjunction with Salmonella therapy. These findings suggested that IL-1β and TNF-α play important roles in Salmonella-mediated cancer therapy. A better understanding of host immune responses in Salmonella therapy may increase the success of a given drug, particularly when various strategies are combined with bacteriotherapy.
authors.affiliation: 3. School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Republic of Korea ; 4. Academy of Immunology and Microbiology (AIM), Institute of Basic Science (IBS), Pohang, Republic of Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: 1. Laboratory of In Vivo Molecular Imaging, Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Gwangju, Republic of Korea.
authors.forename: Thuy Xuan
authors.initials: TX
authors.lastname: Phan
authors.affiliation: 1. Laboratory of In Vivo Molecular Imaging, Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Gwangju, Republic of Korea.
authors.forename: Vu Hong
authors.initials: VH
authors.lastname: Nguyen
authors.affiliation: 1. Laboratory of In Vivo Molecular Imaging, Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Gwangju, Republic of Korea.
authors.forename: Hong-Van
authors.initials: HV
authors.lastname: Dinh-Vu
authors.affiliation: 1. Laboratory of In Vivo Molecular Imaging, Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Gwangju, Republic of Korea.
authors.forename: Jin Hai
authors.initials: JH
authors.lastname: Zheng
authors.affiliation: 1. Laboratory of In Vivo Molecular Imaging, Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Gwangju, Republic of Korea.
authors.forename: Misun
authors.initials: M
authors.lastname: Yun
authors.affiliation: 3. School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Sung-Gyoo
authors.initials: SG
authors.lastname: Park
authors.affiliation: 2. Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Yeongjin
authors.initials: Y
authors.lastname: Hong
authors.affiliation: 2. Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Hyon E
authors.initials: HE
authors.lastname: Choy
authors.affiliation: 5. Fraunhofer IZI, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Szardenings
authors.affiliation: 3. School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Republic of Korea ; 4. Academy of Immunology and Microbiology (AIM), Institute of Basic Science (IBS), Pohang, Republic of Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Hwang
authors.affiliation: 4. Academy of Immunology and Microbiology (AIM), Institute of Basic Science (IBS), Pohang, Republic of Korea.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Park
authors.affiliation: 4. Academy of Immunology and Microbiology (AIM), Institute of Basic Science (IBS), Pohang, Republic of Korea.
authors.forename: SunHee
authors.initials: S
authors.lastname: Park
authors.affiliation: 4. Academy of Immunology and Microbiology (AIM), Institute of Basic Science (IBS), Pohang, Republic of Korea ; 6. Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea.
authors.forename: Sin-Hyeog
authors.initials: SH
authors.lastname: Im
authors.affiliation: 1. Laboratory of In Vivo Molecular Imaging, Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Gwangju, Republic of Korea ; 2. Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology; D053583:Interleukin-1beta / Q000032:analysis*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D012486:Salmonella typhimurium / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: Bacteria-mediated cancer therapy; E. coli; IL-1β; Salmonella typhimurium; TNF-α; dendritic cells