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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Live Biotherapeutic Lactococcus lactis GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System.
Live Biotherapeutic Lactococcus lactis GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System.
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肠道微生物群通过调节宿主免疫系统和肿瘤微环境,导致抗癌药物疗效存在差异。有趣的是,这种差异效应具有高度菌株特异性。例如,某些菌株可以直接抑制肿瘤生长并增强抗肿瘤免疫;然而,其他菌株则没有这种效果,甚至促进肿瘤生长。鉴定具有抗肿瘤效果的有效菌株是开发活体生物治疗抗癌产品的关键。在此,我们发现乳酸乳球菌GEN3013通过调节肿瘤血管生成和直接诱导癌细胞死亡来抑制肿瘤生长。此外,乳酸乳球菌GEN3013增强了奥沙利铂和PD-1阻断的治疗效果。全面的免疫分析显示,乳酸乳球菌GEN3013增加了肿瘤微环境中的细胞毒性免疫细胞群体,如CD4 + T细胞、CD8 + 效应T细胞和NK细胞。我们的结果表明,乳酸乳球菌GEN3013是一种有前景的候选菌株,可与当前标准疗法联合增强癌症治疗。
The gut microbiota is responsible for differential anticancer drug efficacies by modulating the host immune system and the tumor microenvironment. Interestingly, this differential effect is highly strain-specific. For example, certain strains can directly suppress tumor growth and enhance antitumor immunity; however, others do not have such an effect or even promote tumor growth. Identifying effective strains that possess antitumor effects is key for developing live biotherapeutic anticancer products.
Here, we found that Lactococcus lactis GEN3013 inhibits tumor growth by regulating tumor angiogenesis and directly inducing cancer cell death.
Moreover, L. lactis GEN3013 enhanced the therapeutic effects of oxaliplatin and the PD-1 blockade. Comprehensive immune profiling showed that L. lactis GEN3013 augmented cytotoxic immune cell populations, such as CD4 + T cells, CD8 + effector T cells, and NK cells in the tumor microenvironment.
Our results indicate that L. lactis GEN3013 is a promising candidate for potentiating cancer treatment in combination with current standard therapy.
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