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:Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice.
Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice.
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以PD-L1为靶点的免疫检查点阻断已在癌症治疗中取得突破。尽管基于抗PD-L1的免疫治疗已被批准为多种癌症类型的标准疗法,但由于对免疫治疗的低应答,其在大多数结直肠癌(CRC)中的治疗效果仍然有限。
因此,将治疗与草药联合使用可能是治疗CRC以克服这一局限的替代方法。补中益气汤(BJIKT)是一种用于传统中医的草药方剂,在临床上可改善癌症患者的生活质量,并具有抗肿瘤和免疫调节活性。
然而,BJIKT对肿瘤微环境中免疫应答的调节作用在很大程度上仍未得到研究。在本研究中,我们在MC38 CRC荷瘤C57BL/6小鼠模型中验证了BJIKT对肿瘤生长的抑制作用,并研究了BJIKT与抗PD-L1联合治疗对抗肿瘤免疫应答的调节作用。通过流式细胞术进行免疫谱分析,以表征参与抗癌活性的确切细胞类型。BJIKT与抗PD-L1治疗的联合治疗显著抑制了MC38荷瘤小鼠的肿瘤生长,并增加了肿瘤组织中细胞毒性T淋巴细胞和NK 细胞的比例。
此外,BJIKT抑制了髓源性抑制细胞群体,表明这种联合治疗通过改善肿瘤微环境有效调节T细胞的免疫功能。草药方剂BJIKT可作为一种新的治疗选择,用于改善CRC患者基于抗PD-L1的免疫治疗。
Immune checkpoint blockage targeting PD-L1 has led to breakthroughs in cancer treatment. Although anti-PD-L1-based immunotherapy has been approved as standard therapy in various cancer types, its therapeutic efficacy in most colorectal cancers (CRC) is still limited due to the low response to immunotherapy.
Therefore, combining treatment with herbal medicines could be an alternative approach for treating CRC to overcome this limitation. Bojungikki-Tang (BJIKT), a herbal formula used in traditional Chinese medicine, clinically improves the quality of life for cancer patients and has been associated with antitumor and immune-modulating activities.
However, the regulatory effect of BJIKT on the immune response in the tumor microenvironment remains largely uninvestigated. In this study, we verified the inhibitory effect of BJIKT on tumor growth and investigated the regulatory effect of combination therapy with BJIKT and anti-PD-L1 on antitumor immune responses in an MC38 CRC-bearing C57BL/6 mouse model.
Immune profiling analysis by flow cytometry was used to characterize the exact cell types contributing to anticancer activities. Combination treatment with BJIKT and anti-PD-L1 therapy significantly suppressed tumor growth in MC38-bearing mice and increased the proportion of cytotoxic T lymphocytes and natural killer cells in tumor tissues.
Furthermore, BJIKT suppressed the population of myeloid-derived suppressor cells, suggesting that this combination treatment effectively regulates the immunological function of T-cells by improving the tumor microenvironment. The herbal formula BJIKT can be a novel therapeutic option for improving anti-PD-L1-based immunotherapy in patients with CRC.
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