RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
英文原题:Enhancing melanoma treatment through systemic delivery of an immune boosting Staphylococcus epidermidis strain.
Enhancing melanoma treatment through systemic delivery of an immune boosting Staphylococcus epidermidis strain.
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在我们之前的研究中发现的一种独特的表皮葡萄球菌菌株 AIT01(AIT,气道免疫训练菌),已显示出免疫增强特性。本研究旨在评估这种免疫增强型皮肤微生物群菌株的全身免疫调节作用和潜在抗肿瘤特性。
我们进行了一系列离体和体内实验,以评估免疫细胞增殖、细胞因子产生和抗肿瘤疗效。在离体研究中,经该菌株的细菌裂解物或培养上清处理的脾细胞显示出以浓度依赖性方式显著增加的活力。流式细胞术分析显示,在裂解物处理组中,树突状细胞、NK 细胞和 γδ T 细胞群体增加,细胞因子产生增强,尤其是 IFN-γ(干扰素-γ)和穿孔素。当在体内通过腹腔和静脉途径给药时,小鼠在接受细菌裂解物后显示出对黑色素瘤生长的显著抑制。
值得注意的是,预处理显示出优于后处理的疗效。此外,与抗 PD-1(抗程序性细胞死亡蛋白-1)单克隆抗体联合使用,与抗 PD-1 单药治疗相比,进一步抑制了肿瘤生长。这些发现表明,AIT01 裂解物增强免疫细胞增殖和细胞因子产生,从而有助于其强效抗肿瘤作用。这种免疫增强型皮肤微生物群菌株的全身递送,特别是与抗 PD-1 疗法联合使用,有望成为对抗黑色素瘤的有效免疫治疗策略。
A unique strain of Staphylococcus epidermidis, AIT01 (AIT, Airway Immune Trainer), identified in our previous research, has demonstrated immune-boosting properties.
This study aimed to evaluate the systemic immune-modulatory effects and potential anti-tumor properties of this immune-enhancing skin microbiota strain. A series of ex vivo and in vivo experiments were conducted to assess immune cell proliferation, cytokine production, and anti-tumor efficacy. In ex vivo studies, splenocytes treated with the bacterial lysate or culture supernatant of the strain showed significantly increased viability in a concentration-dependent manner.
Flow cytometry analysis revealed increased populations of dendritic cells, NK cells (Natural killer cells), and γδ T cells, with enhanced cytokine production, particularly IFN-γ (Interferon-γ) and perforin, in the lysate-treated group. When administered via intraperitoneal and intravenous routes in vivo, mice showed significant inhibition of melanoma growth upon receiving the bacterial lysate.
Notably, pre-treatment demonstrated superior efficacy compared to post-treatment.
Furthermore, the combination of the bacterial lysate with anti-PD-1 (anti-Programmed cell death protein-1) monoclonal antibody further suppressed tumor growth compared to anti-PD-1 monotherapy.
These findings suggest that the AIT01 lysate enhances immune cell proliferation and cytokine production, contributing to its potent anti-tumor effects. The systemic delivery of this immune-boosting skin microbiota strain, particularly in combination with anti-PD-1 therapy, holds promise as an effective immunotherapeutic strategy against melanoma.
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