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首页> 美国卫生研究院文献>Oncology Letters >T cell immunity induced by a bivalent Salmonella-based CEACAM6 and 4-1BBL vaccines in a rat colorectal cancer model
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T cell immunity induced by a bivalent Salmonella-based CEACAM6 and 4-1BBL vaccines in a rat colorectal cancer model

机译：基于二价沙门氏菌的CEACAM6和4-1BBL疫苗在大鼠大肠癌模型中诱导的T细胞免疫

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The present study investigated the anti-tumor mechanisms of recombinant non-specific cross-reacting antigen (CEACAM6) and 4-1BB ligand (4–1BBL) Salmonella-based vaccines, and the effect that these vaccinations have on memory T cells and T helper (Th) cell polarization. Colon tumors were induced in rats via 1,2-dimethylhydrazine (DMH) injections. Rats were then treated with injections of attenuated Salmonella typhimurium carrying pIRES-CEACAM6, pIRES-4-1BBL or pIRES-CEACAM6-4-1BBL. In total, 4 vaccine injections, one every other week, were administered during the 8 weeks subsequent to the DMH injection. Rats were sacrificed 18 weeks subsequent to the DMH injections, and the colons and spleens were collected for further analysis. Cluster of differentiation (CD) 45RO, interleukin (IL)-4 and IL-17 expression was analyzed in colon tumor tissues, and the expression of interferon (IFN)-γ, CD3+, CD4+, CD8+, CD56+, forkhead/winged-helix transcription factor box P3 (FOXP3+), IL-4 and IL-17 were analyzed in splenic tissues. Compared with the pIRES/SL3261 group, the pIRES-CEACAM6-4-1BBL/SL3261 treatment group had a significantly higher number of CD45RO+ expressing tumor infiltrating lymphocytes and lower expression levels of IL-4 and IL-17. Splenic tissues from the same treatment group exhibited significantly increased expression of IFN-γ, CD3+ and CD8+ and reduced expression levels of Foxp3, IL-4 and IL-7. CD56+ T cell expression was increased in all groups except for the group that received no vaccine. The present study concluded that the combined CEACAM6 and 4-1BBL-attenuated recombinant Salmonella vaccine was able to inhibit the growth of DMH-induced colorectal tumors. This was mediated by generating an anti-tumor immune response, increasing the number of of CD45RO+ memory T cells, decreasing the number of FOXP3+ cells and promoting Th1 polarization.
机译：本研究调查了基于重组非特异性交叉反应抗原（CEACAM6）和4-1BB配体（4-1BBL）沙门氏菌的疫苗的抗肿瘤机制，以及这些疫苗对记忆性T细胞和T辅助物的影响（Th）细胞极化。通过1,2-二甲基肼（DMH）注射在大鼠中诱发结肠肿瘤。然后用携带pIRES-CEACAM6，pIRES-4-1BBL或pIRES-CEACAM6-4-1BBL的减毒鼠伤寒沙门氏菌注射治疗大鼠。在DMH注射后的8周内，总共每隔一周注射4次疫苗。在注射DMH后18周处死大鼠，并收集结肠和脾脏用于进一步分析。分析结肠肿瘤组织中分化簇（CD）45RO，白介素（IL）-4和IL-17的表达，并分析干扰素（IFN）-γ，CD3 +，CD4 +，CD8 +，CD56 +，前叉/翼状螺旋的表达在脾组织中分析了转录因子盒P3（FOXP3 +），IL-4和IL-17。与pIRES / SL3261组相比，pIRES-CEACAM6-4-1BBL / SL3261治疗组的CD45RO +表达肿瘤浸润淋巴细胞的数量明显更高，而IL-4和IL-17的表达水平则较低。来自同一治疗组的脾组织显示IFN-γ，CD3 +和CD8 +的表达显着增加，而Foxp3，IL-4和IL-7的表达水平降低。除未接种疫苗的组外，所有组的CD56 + T细胞表达均增加。本研究得出结论，CEACAM6和4-1BBL减毒重组沙门氏菌疫苗的组合能够抑制DMH诱导的结直肠肿瘤的生长。这是通过产生抗肿瘤免疫应答，增加CD45RO +记忆T细胞的数量，减少FOXP3 +细胞的数量并促进Th1极化来介导的。

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