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:An in vitro model to monitor natural killer cell effector functions against breast cancer cells derived from human tumor tissue.
An in vitro model to monitor natural killer cell effector functions against breast cancer cells derived from human tumor tissue.
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基于过继性自然杀伤(NK)细胞的免疫治疗是一种有前景的癌症治疗方法。尽管NK细胞输注相关毒性极小,但NK细胞治疗的潜力受到免疫抑制性肿瘤微环境(TME)的限制。目前正在研究多种改善抗癌NK细胞效应功能的方法。虽然目前大部分临床前研究使用市售肿瘤细胞系进行,但这种方法缺乏TME的影响以及患者原发肿瘤的异质性。在此,我们描述了一套针对原发乳腺癌组织来源肿瘤细胞的NK细胞细胞毒性和脱颗粒检测的综合方案。在此模型中,可以实施增强NK细胞抗肿瘤效应功能的处理。此外,通过在后续检测中使用培养上清液,或在共培养系统中加入其他细胞类型,可以研究进一步协调固有免疫和适应性免疫的其他NK细胞效应机制。
Adoptive natural killer (NK) cell-based immunotherapy poses a promising treatment approach in cancer. Despite minimal toxicities associated with NK cell infusion, the potential of NK cell therapy is inhibited by the immunosuppressive tumor microenvironment (TME).
Multiple approaches to improve anti-cancer NK cell effector functions are being investigated. While much of this preclinical research is currently performed with commercially available tumor cell lines, this approach lacks the influence of the TME and heterogeneity of the primary tumor in patients.
Here, we describe a comprehensive protocol for NK cell cytotoxicity- and degranulation assays against tumor cells derived from primary breast cancer tissue. Treatments to boost NK cell anti-tumor effector functions can be implemented in this model.
Moreover, by using culture supernatants in follow up assays or by including additional cell types in the co-culture system, other NK cell effector mechanisms that further orchestrate innate and adaptive immunity could be studied.
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