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Tumor-Targeting Salmonella typhimurium A1-R Promotes Tumoricidal CD8+ T Cell Tumor Infiltration and Arrests Growth and Metastasis in a Syngeneic Pancreatic-Cancer Orthotopic Mouse Model.

Authors
 Takashi Murakami  ;  Yukihiko Hiroshima  ;  Yong Zhang  ;  Ming Zhao  ;  Tasuku Kiyuna  ;  Ho Kyoung Hwang  ;  Kentaro Miyake  ;  Yuki Homma  ;  Ryutaro Mori  ;  Ryusei Matsuyama  ;  Takashi Chishima  ;  Yasushi Ichikawa  ;  Kuniya Tanaka  ;  Michael Bouvet  ;  Itaru Endo  ;  Robert M. Hoffman 
Citation
 JOURNAL OF CELLULAR BIOCHEMISTRY, Vol.119(1) : 634-639, 2018 
Journal Title
 JOURNAL OF CELLULAR BIOCHEMISTRY 
ISSN
 0730-2312 
Issue Date
2018
MeSH
Adenocarcinoma/immunology ; Adenocarcinoma/pathology ; Adenocarcinoma/therapy* ; Animals ; CD8-Positive T-Lymphocytes/immunology* ; CD8-Positive T-Lymphocytes/pathology ; Immunity, Cellular* ; Immunotherapy* ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/pathology ; Neoplasms, Experimental/therapy* ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/therapy* ; Salmonella typhimurium/immunology*
Keywords
C57BL/6 MICE ; CD8+ T CELLS ; METASTASIS ; ORTHOTOPIC MOUSE MODEL ; PANCREATIC CANCER ; Salmonella typhimurium A1-R ; TUMOR INFILTRATION
Abstract
The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8+ tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8+ TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1-R-treatment group (n = 8, 1 × 107 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P < 0.01). Hematoxylin and easin (H&E) staining on tumor sections was performed to evaluate tumor destruction which was classified according to the Evans grading system and found to be much greater in the S. typhimurium A1-R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P < 0.01). Immunohistochemical staining with anti-mouse CD8+ antibody was performed in order to detect TILs determined by calculating the average number of CD8+ cells in three high power fields (200×) in the treated and untreated tumors. The TIL score was significantly higher in G2 (133.5 ± 32.2) than G1 (45.1 ± 19.4, P < 0.001). The present study demonstrates that S. typhimurium A1-R promotes CD8+ T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018.
Full Text
https://onlinelibrary.wiley.com/doi/full/10.1002/jcb.26224
DOI
10.1002/jcb.26224
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Hwang, Ho Kyoung(황호경) ORCID logo https://orcid.org/0000-0003-4064-7776
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165439
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