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:Anlotinib and anti-PD-1 mAbs perfected CIK cell therapy for lung adenocarcinoma in preclinical trials.
Anlotinib and anti-PD-1 mAbs perfected CIK cell therapy for lung adenocarcinoma in preclinical trials.
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小鼠细胞因子诱导的杀伤(CIK)细胞是异体细胞,可杀伤多种同种异体和同基因肿瘤,并具有NK 细胞和T淋巴细胞的功能和表型特征。
然而,单独使用CIK细胞治疗实体瘤的效果有限。为了增强治疗效果,发现多种治疗方法的联合至关重要。异常肿瘤血管和肿瘤微环境会抑制免疫细胞功能,阻碍淋巴细胞进入肿瘤组织。为提高CIK细胞抗肿瘤活性的有效性,可将抗血管治疗与CIK细胞治疗联合使用。
此外,安罗替尼是一种多靶点酪氨酸激酶抑制剂的小分子药物,可阻断细胞迁移、延缓血管生成并降低血管密度。与其他抗血管生成药物相比,安罗替尼因作用靶点更广、有效剂量更低而脱颖而出。
在本研究中,将安罗替尼与小鼠CIK细胞联合使用,可增强CD3+ T细胞浸润、CD3+CD4+ T细胞浸润以及CD3+CD8+ T细胞中颗粒酶B和干扰素γ的表达,从而增强抗肿瘤活性。通过T淋巴细胞产生细胞毒性细胞因子,使用抗PD-1单克隆抗体联合安罗替尼和CIK细胞的治疗组比接受双联治疗的组更有效。该临床前研究有助于探索肺腺癌患者的治疗选择,从而延长其生命。
Murine cytokine-induced killer (CIK) cells are heterologous cells that kill various allogeneic and isogenic tumors and have functional and phenotypic characteristics of natural killer cells and T lymphocytes.
However, the effect of CIK cells alone on solid tumor therapy is only limited. To enhance the therapeutic effect, it is vital to discover a mix of several therapy approaches. Immune cell function is inhibited by abnormal tumor vessels and the tumor microenvironment, which block lymphocyte entry into tumor tissue. To increase the effectiveness of CIK cells' antitumor activity, antivascular therapy and CIK cell therapy can be combined.
Furthermore, anlotinib is a tiny drug with multitarget tyrosine kinase inhibitors that can block cell migration, delay angiogenesis, and decrease blood vessel density. Compared with other antiangiogenesis drugs, anlotinib stands out due to the wider target of action and lower effective dose. In this work, anlotinib and murine CIK cells were coupled to boost CD3+ T cell infiltration, CD3+CD4+ T cell infiltration, and expression of granzyme B and interferon γ from CD3+CD8+ T cells, which increased the antitumor activity.
Through the generation of cytotoxic cytokines by T lymphocytes, the therapeutic group using anti-PD-1 monoclonal antibodies in conjunction with anlotinib and CIK cells was more successful than the group receiving dual therapy. The preclinical study contributes to exploring the therapeutic alternatives for patients with lung adenocarcinoma, thus prolonging their lives.
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