Background. The drug resistance and the immune suppression in the tumor microenvironment are important factors affecting tumor progression. Reversing drug resistance and changing tumor suppression microenvironment are ideal ways to inhibit tumor progression. Objective. The aim of the study is to verify antitumor immune response of probiotics in patients with colorectal carcinoma and to explore its mechanism. Methods. To detect the tumor samples of 122 patients with colorectal carcinoma after surgery, analyze the effect of probiotics on enhancing tumor-infiltrating CD8⁺T cells to inhibit colorectal carcinoma, and further verify the mechanism of probiotics on enhancing the antitumor immune response of CD8⁺T cells through animal experiments. Results. The results of immunohistochemistry showed that the proportion of CD8⁺T cells in the patients treated with probiotics before surgery was increased significantly than that in other patients (). The results of flow cytometry also showed that the proportion of CD8⁺T cells in the probiotics group was higher than that in the nonprobiotics group (). Kaplan-Meier survival estimates also showed that the CD8⁺T cells, TNM stage, pathology grade, lymphatic metastasis, and probiotic treatment were significantly associated with the progression-free survival (PFS) (, for CD8⁺T cells; , for TNM stage; , for pathology grade; , for Lymphatic metastasis; and , for the group (group A was treated with probiotics before surgery; group B was not treated with probiotics)). The experimental results in mice showed that probiotics could inhibit tumor growth and increase the proportion of CD8⁺T cells in mice; the difference was statistically significant (). It was also found that probiotic feeding could upregulate the expression of T-cell immunoglobulin mucin receptor 1(TIM-1) in CD8⁺T cells of mice and also found that probiotic feeding could downregulate the expression of programmed cell death protein 1 (PD-1) in CD8⁺T cells of mice, compared with the nonfeeding group; the difference was statistically significant ( for TIM-1 and for PD-1, respectively). In order to further understand the functional status of CD8⁺T cells, we analyzed interferon-gamma (IFN-γ)⁺ T cells and tumor necrosis factor-α (TNF-α)⁺CD8⁺T cells by flow cytometry. The results showed that the proportion of IFN-γ⁺ T cells and TNF-α⁺CD8⁺T cells significantly increased after probiotic treatment, compared with the nonprobiotic treatment group; the difference was statistically significant ( for IFN-γ⁺ T cells and for TNF-α⁺CD8⁺T, respectively). Conclusions. Probiotics can enhance the antitumor immune response of CD8⁺T cells. It can play a synergistic antitumor role. On the one hand, its mechanism is through regulating intestinal flora, and on the other hand, through regulating the antitumor immune function of CD8⁺T cells.

中文翻译：

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益生菌可增强 BALB/c 小鼠和结直肠癌患者 CD8+T 细胞的抗肿瘤免疫力。

背景。肿瘤微环境中的耐药性和免疫抑制是影响肿瘤进展的重要因素。逆转耐药性和改变肿瘤抑制微环境是抑制肿瘤进展的理想方法。客观。本研究旨在验证益生菌对结直肠癌患者的抗肿瘤免疫反应，并探讨其作用机制。方法。对122例大肠癌术后肿瘤样本进行检测，分析益生菌增强肿瘤浸润CD8 ⁺ T细胞抑制大肠癌的作用，进一步验证益生菌增强CD8 ^{+抗肿瘤免疫反应的机制}T细胞通过动物实验。结果。免疫组化结果显示，术前接受益生菌治疗的患者CD8 ^{+ T细胞比例显着高于其他患者。}）。流式细胞仪检测结果还显示，益生菌组CD8 ⁺ T细胞比例高于非益生菌组。）。Kaplan-Meier 生存期估计还显示，CD8 ⁺ T 细胞、TNM 分期、病理分级、淋巴转移和益生菌治疗与无进展生存期 (PFS) 显着相关。, 对于 CD8 ⁺ T 细胞；, TNM阶段；, 病理级；, 用于淋巴转移；和, 组（A组术前用益生菌治疗；B组未用益生菌治疗））。小鼠实验结果表明，益生菌可以抑制肿瘤生长，增加小鼠CD8 ⁺ T细胞比例；差异有统计学意义（）。还发现益生菌喂养可以上调小鼠CD8 ⁺ T细胞T细胞免疫球蛋白粘蛋白受体1（TIM-1）的表达，同时发现益生菌喂养可以下调程序性细胞死亡蛋白1（PD- 1) 在小鼠的 CD8 ⁺ T 细胞中，与非喂养组相比；差异有统计学意义（对于 TIM-1 和分别用于 PD-1）。为了进一步了解CD8 ⁺ T细胞的功能状态，我们通过流式细胞仪分析了干扰素-γ（IFN- γ）⁺ T细胞和肿瘤坏死因子-α（TNF -α）⁺ CD8 ^{+ T细胞。}结果显示，与非益生菌治疗组相比，益生菌治疗后IFN- γ ⁺ T细胞和TNF - α ⁺ CD8 ^{+ T细胞的比例显着增加；}差异有统计学意义（对于 IFN- γ ⁺ T 细胞和对于 TNF -α ⁺ CD8 ⁺ T，分别）。结论。益生菌可以增强CD8 ⁺ T细胞的抗肿瘤免疫反应。可起到协同抗肿瘤作用。其作用机制一方面是通过调节肠道菌群，另一方面是通过调节CD8 ⁺ T细胞的抗肿瘤免疫功能。