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:Combinatorial immunotherapy with gemcitabine and ex vivo-expanded NK cells induces anti-tumor effects in pancreatic cancer.
Combinatorial immunotherapy with gemcitabine and ex vivo-expanded NK cells induces anti-tumor effects in pancreatic cancer.
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胰腺癌在初期难以诊断,通常在转移到附近器官后才被发现。吉西他滨目前被用作胰腺癌的标准治疗。然而,由于胰腺癌的化疗尚未达到令人满意的治疗效果,因此尝试了辅助化疗方法。可以预期,将免疫细胞疗法与现有的抗癌药物联合治疗相结合,将能预防癌症复发并提高生存率。我们分离了自然杀伤(NK)细胞,并将其与强激活的自体外周血单核细胞(PBMCs)作为饲养细胞共培养,使用CD3抗体、IFN-r、IL-2和γ辐射进行激活。与静息NK细胞相比,通过这种方法扩增的NK细胞在与胰腺癌细胞系共培养时表现出更强的细胞毒性。在胰腺癌小鼠异种移植模型中,肿瘤生长被有效抑制。通过联合使用吉西他滨和厄洛替尼,治疗效果得到提高。这些发现表明,通过本文提出的方法培养的NK细胞具有优异的抗肿瘤活性。我们证明,激活的NK细胞与基于吉西他滨的治疗联合使用时,能够有效抑制胰腺肿瘤。
Pancreatic cancer is difficult to diagnose at the initial stage and is often discovered after metastasis to nearby organs. Gemcitabine is currently used as a standard treatment for pancreatic cancer.
However, since chemotherapy for pancreatic cancer has not yet reached satisfactory therapeutic results, adjuvant chemotherapy methods are attempted. It can be expected that combining immune cell therapy with existing anticancer drug combination treatment will prevent cancer recurrence and increase survival rates.
We isolated natural killer (NK) cells and co-cultured them with strongly activated autologous peripheral blood mononuclear cells (PBMCs) as feeder cells, activated using CD3 antibody, IFN-r, IL-2, and γ-radiation. NK cells expanded in this method showed greater cytotoxicity than resting NK cells, when co-cultured with pancreatic cancer cell lines. Tumor growth was effectively inhibited in a pancreatic cancer mouse xenograft model. Therapeutic efficacy was increased by using gemcitabine and erlotinib in combination.
These findings suggest that NK cells cultured by the method proposed here have excellent anti-tumor activity.
We demonstrate that activated NK cells can efficiently inhibit pancreatic tumors when used in combination with gemcitabine-based therapy.
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