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.
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.
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在同基因胰腺癌原位小鼠模型中，靶向肿瘤的鼠伤寒沙门氏菌 A1-R 促进杀肿瘤 CD8 T 细胞肿瘤浸润并阻止生长和转移。
DOI：
10.1002/jcb.26224
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Hoffman RM.
中科院分区：
文献类型：
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作者：
Murakami T;Hiroshima Y;Zhang Y;Zhao M;Kiyuna T;Hwang HK;Miyake K;Homma Y;Mori R;Matsuyama R;Chishima T;Ichikawa Y;Tanaka K;Bouvet M;Endo I;Hoffman RM.
本研究确定了肿瘤靶向菌株鼠伤寒沙门氏菌A1-R（S.typhimuriumA1-R）对同基因胰腺癌原位小鼠模型中CD8+肿瘤浸润淋巴细胞（TIL）的影响。肿瘤靶向作用S. CD8+TIL 上的鼠伤寒 A1-R 是在原位植入 C57BL/6 免疫功能低下小鼠胰尾的 Pan02 小鼠胰腺腺癌上测定的。原位植入三周后，将小鼠随机分组如下 G1：未治疗对照组（n = 8）；和G2：S。鼠伤寒A1-R治疗组（n = 8，1 × 107菌落形成单位[CFU]/身体，静脉注射，每周，3周）。在初始治疗的第22天，处死所有小鼠并收获肿瘤。肿瘤体积比定义为第22天肿瘤体积相对于第1天的肿瘤体积之比。 S组的肿瘤体积比显着较低。鼠伤寒A1-R治疗组（G2）（3.0±2.8）高于未治疗对照组（G1）（39.9±30.7，P<0.01）。对肿瘤切片进行苏木精和 easin (H&E) 染色以评估肿瘤破坏，根据 Evans 分级系统对肿瘤破坏进行分类，发现 S 中的肿瘤破坏程度要大得多。鼠伤寒A1-R处理小鼠（G2）。 G1 期有 6 只小鼠出现腹膜播散，而 G2 期无小鼠出现腹膜播散（P< 0.01）。使用抗小鼠 CD8+ 抗体进行免疫组织化学染色，以检测经过治疗和未治疗的肿瘤中三个高倍视野 (200×) 中 CD8+ 细胞的平均数量，从而检测 TIL。 G2组TIL评分(133.5±32.2)显着高于G1组(45.1±19.4,P<0.001)。本研究表明 S.鼠伤寒A1-R促进CD8+T细胞浸润并抑制肿瘤生长和转移。 J.细胞。生物化学。 119: 634–639, 2018。© 2017 Wiley periodicals, Inc.
The present study determined the effect of the tumor‐targeting strainSalmonella typhimuriumA1‐R (S. typhimuriumA1‐R) on CD8+tumor‐infiltrating lymphocytes (TILs) in a syngeneic pancreatic‐cancer orthotopic mouse model. The effect of tumor‐targetingS. typhimuriumA1‐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. typhimuriumA1‐R‐treatment group (n = 8, 1 × 107colony 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 theS. typhimuriumA1‐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 theS. typhimuriumA1‐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 thatS. typhimuriumA1‐R promotes CD8+T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634–639, 2018. © 2017 Wiley Periodicals, Inc.