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:AHCC(®), a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer.
AHCC(®), a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer.
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将ICB与其他药物联合的治疗策略已成为癌症治疗中一种有前景的方法。AHCC ® 是一种标准化的培养香菇菌丝体提取物,据报道可抑制肿瘤生长并增强免疫细胞功能。在此,我们研究了AHCC ® 是否促进癌症免疫治疗的治疗效果。与水和DICB联合治疗相比,口服AHCC ® 联合双重免疫检查点阻断(DICB),包括PD-1/CTLA-4阻断,在MC38结肠癌荷瘤小鼠中减少了肿瘤生长,并增加了肿瘤浸润CD8 + T细胞中granzyme B和Ki-67的表达。在相同的荷瘤小鼠中,AHCC ® 和DICB治疗还改变了肠道微生物组的组成,增加了与免疫治疗疗效提高相关的Ruminococcaceae科物种的丰度。在接受抗生素治疗的MC38荷瘤小鼠中未发现AHCC ® 和DICB的抗肿瘤作用。这些数据表明,AHCC ® 通过增强T细胞功能和影响肠道微生物组来增加DICB的抗肿瘤作用。
Treatment strategies combining immune checkpoint blockade (ICB) with other agents have emerged as a promising approach in the treatment of cancers. AHCC ® , a standardized extract of cultured Lentinula edodes mycelia, has been reported to inhibit tumor growth and enhance immune cell function.
Here we investigated whether AHCC ® promotes the therapeutic effect of immunotherapy in cancers. A combination of oral AHCC ® and dual immune checkpoint blockade (DICB), including PD-1/CTLA-4 blockade, had reduced tumor growth and increased granzyme B and Ki-67 expression by tumor-infiltrating CD8 + T cells in MC38 colon cancer bearing mice compared to a combination of water and DICB.
In the same tumor bearing mice, AHCC ® and DICB treatment also altered the composition of the gut microbiome with the increased abundance of the species of Ruminococcaceae family which is associated with increased therapeutic efficacy of immunotherapy. The anti-tumor effect of AHCC ® and DICB was not found in MC38 tumor-bearing mice treated with antibiotics. These data suggest that AHCC ® increases the anti-tumor effect of DICB by enhancing T cell function and affecting the gut microbiome.
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