Recombinant Salmonella-based CEACAM6 and 4-1BBL vaccine enhances T-cell immunity and inhibits the development of colorectal cancer in rats: In vivo effects of vaccine containing 4-1BBL and CEACAM6
Recombinant Salmonella-based CEACAM6 and 4-1BBL vaccine enhances T-cell immunity and inhibits the development of colorectal cancer in rats: In vivo effects of vaccine containing 4-1BBL and CEACAM6
复制标题
基于沙门氏菌的重组 CEACAM6 和 4-1BBL 疫苗增强 T 细胞免疫并抑制大鼠结直肠癌的发展：含有 4-1BBL 和 CEACAM6 的疫苗的体内效果。
DOI：
10.3892/or.2015.3901
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发表时间：
2015-06-01
期刊：
影响因子：
4.2
通讯作者：
Chen, Weichang
中科院分区：
文献类型：
--
作者：
Jin, Chunhui;Liu, Yingying;Chen, Weichang
本研究旨在探讨基于沙门氏菌（SL 3261）的CEACAM 6和4-1BB配体（4-1BBL）重组疫苗对大鼠结直肠癌发生的影响及其可能的免疫机制。构建了携带质粒pIRES-CEACAM 6、pIRES-4 - 1BBL和pIRES-CEACAM 6 -4-1BBL的减毒鼠伤寒沙门氏菌（疫苗株）。给大鼠皮下注射1，2-二甲基肼（DMH），每周1次，共18周。第1次注射后8周，将大鼠分为pIRES/SL 3261、pIRES-4-1BBL/SL 3261、pIRES-CEACAM 6/SL 3261和pIRES-CEACAM 6 -4-1BBL/SL 3261组，分别给予相应的疫苗株喂养。然后处死大鼠，记录结肠肿瘤的数量，并评估Dukes分期。免疫组化法检测肿瘤组织中CD 3、CD 4、CD 8、CD 56、FOXP 3和CEACAM 6的表达。与pIRES/SL 3261组中的表达水平相比，鉴定了pIRES-CEACAM 6/SL 3261组大鼠的类似水平的CD 3+、CD 8+和CD 56+表达。此外，在pIRES-4-1BBL/SL 3261和pIRES-CEACAM 6/SL 3261组中检测到相当数量的肿瘤。相比之下，在pIRES-CEACAM 6 -4-1BBL/SL 3261组大鼠中检测到显著较少数量的肿瘤，尽管具有较高密度的CD 3 + CD 8+、CD 56+和较低密度的Foxp 3+肿瘤浸润淋巴细胞（TIL）细胞。结果表明，携带CEACAM 6和4-1BBL基因的重组减毒沙门氏菌能有效地提高CD 3 + CD 8 + TIL和NK细胞的数量，降低FOXP 3细胞的数量，抑制DMH诱导的大鼠大肠癌的发生。
The present study aimed to determine the effect of recombinant Salmonella (SL3261)-based CEACAM6 and 4-1BB ligand (4-1BBL) vaccine on the development of colorectal cancer in rats and the potential immune mechanisms involved. Attenuated Salmonella typhimurium (vaccine strain)‑carrying plasmids pIRES-CEACAM6, pIRES‑4‑1BBL and pIRES-CEACAM6-4-1BBL were constructed. The rats were administered subcutaneous injections of 1,2-dimethyl-hydrazine (DMH) once a week for 18 weeks. Eight weeks after the first injection, the rats were divided into the pIRES/SL3261, pIRES-4-1BBL/SL3261, pIRES-CEACAM6/SL3261 and pIRES-CEACAM6-4-1BBL/SL3261 groups, and fed with corresponding vaccine strains. The rats were then sacrificed, the number of colon tumors were recorded, and the Dukes' stage were evaluated. CD3, CD4, CD8, CD56, FOXP3 and CEACAM6 expression in tumor tissues was determined by immunohistochemical staining. Compared with the expression levels in the pIRES/SL3261 group, similar levels of CD3+, CD8+ and CD56+ expression were identified for the pIRES-CEACAM6/SL3261 group of rats. Additionally, a comparable number of tumors was detected in the pIRES-4-1BBL/SL3261 and pIRES-CEACAM6/SL3261 groups. By contrast, a significantly fewer number of tumors, albeit with a higher density of CD3+CD8+, CD56+ and a lower density of Foxp3+ tumor-infiltrating lymphocyte (TIL) cells was detected in the pIRES-CEACAM6-4-1BBL/SL3261 group of rats. The results indicated that vaccination with recombinant attenuated Salmonella harboring the CEACAM6 and 4-1BBL gene efficiently increased the number of CD3+CD8+ TIL and NK cells, decreased the number of FOXP3 cells and inhibited the development of DMH-induced colorectal cancer in rats.