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:3M-052 combined inhibitory anti-TNFR2 synergistically suppresses colon cancer progression.
3M-052 combined inhibitory anti-TNFR2 synergistically suppresses colon cancer progression.
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本研究表明,3M-052 与抗 TNFR2 抗体联合使用可发挥协同效应,有效抑制 CRC 进展并诱导长期免疫记忆。总体而言,这些发现支持 MT 联合治疗是一种潜在有效策略的观点。
免疫治疗被认为是实现肿瘤完全清除的最有前景的癌症治疗方法。然而,单一疗法的临床疗效有限,因此越来越多的共识认为,联合免疫治疗——通过多条通路激活免疫系统——似乎是提高治疗效果的最佳策略。在本研究中,我们探讨了联合免疫治疗MT——由TLR7/8激动剂3M-052和抑制性抗TNFR2抗体组成——在结肠癌(CRC)中的疗效及其潜在机制。
建立CRC小鼠模型并分为四组治疗组:对照组、3M-052组、anti-TNFR2组和MT组。每三天监测肿瘤生长情况。采用流式细胞术分析肿瘤组织中CD8+ T细胞和调节性T细胞(Tregs)的水平,以及肿瘤引流淋巴结(TdLNs)中中央记忆T细胞(Tcm)的分化情况。
结果显示,联合治疗MT促进了CD8+ T细胞浸润,降低了肿瘤内Tregs水平,有效抑制了小鼠结肠癌生长,并通过增强TdLNs中Tcm的分化诱导了长期同系肿瘤控制。与单药治疗相比,联合治疗MT在诱导TdLNs中中枢记忆CD8+和CD4+ T细胞分化方面表现出更优的能力,这一效应似乎主要由3M-052介导。
A CRC mouse model was established and divided into four treatment groups: the control group, the 3M-052 group, the anti-TNFR2 group, and the MT group. Tumour growth was monitored every three days. Flow cytometry was used to analyse the levels of CD8+ T cells and regulatory T cells (Tregs) in tumour tissue, as well as the differentiation of central memory T cells (Tcm) in the tumor-draining lymph nodes (TdLNs).
The results revealed that the combination therapy MT promoted CD8+ T cell infiltration and reduced Tregs level within the tumor, effectively suppressed colon cancer growth in mice, and induced long-term syngeneic tumor control by enhancing the differentiation of Tcm in TdLNs. Compared with monotherapy, combination therapy MT demonstrated a superior capacity to induce the differentiation of central memory CD8+ and CD4+ T cells in TdLNs, an effect that appears to be primarily mediated by 3M-052. DISCUSSION: This study demonstrates that the combination of 3M-052 and the anti-TNFR2 antibody exerts a synergistic effect, effectively inhibiting CRC progression and inducing long-term immune memory. Overall, these findings support the view that MT combination therapy represents a potentially effective strategy.
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