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:Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses.
Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses.
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肺癌仍然是全球癌症死亡的主要原因。因此,开发针对这类癌症的策略具有很高的价值。寄生虫感染可与人类较低的癌症发病率相关,并且近年来已在临床前模型中探索了其作为疫苗的用途。
在本研究中,我们探讨了用来自上鞭毛体的克氏锥虫裂解物进行免疫是否能保护小鼠免受肺肿瘤生长的影响。我们还探索了寄生虫聚糖在诱导保护性免疫应答中的作用。
我们使用肺肿瘤细胞系 LL/2 建立了临床前小鼠癌症模型,以评估来自克氏锥虫上鞭毛体的蛋白裂解物在预防性和治疗性设置中的抗肿瘤潜力。用寄生虫裂解物进行免疫可预防肿瘤生长,并诱导针对 LL-2 癌细胞的体液和细胞抗肿瘤免疫应答。所诱导的免疫和肿瘤保护与自然杀伤(NK)细胞的激活、干扰素-γ(IFN-γ)的产生以及肿瘤细胞细胞毒性相关。
我们还表明,克氏锥虫裂解物中的甘露糖残基可诱导 Toll 样受体(TLR)信号传导。所评估的克氏锥虫裂解物具有抗肿瘤特性,可能是通过激活固有免疫和适应性免疫实现的,而在此过程中碳水化合物似乎是必不可少的。
Lung cancer remains the leading cause of cancer mortality worldwide.
Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice.
We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate.
Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-γ (IFN-γ) and tumour cell cytotoxicity.
We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential.
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