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:Cancer and Covid-19: Collectively catastrophic.
Cancer and Covid-19: Collectively catastrophic.
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Covid-19 大流行已在全球迅速蔓延,导致全球超过 300 万人死亡。Covid-19 的症状通常轻微且非特异性,但在某些病例中,患者可能发展为急性呼吸窘迫综合征(ARDS)和全身性炎症。患有炎症性或免疫功能低下疾病(如癌症)的个体更容易发生 ARDS,且死亡率更高。这是通过最初过度刺激的免疫反应介导的,导致促炎细胞因子水平升高,随后引发细胞因子风暴。这加剧了正反馈循环,而抗炎介质无法平衡这些循环。
因此,由 NLRP3 炎症小体激活导致的 IL-1β 水平升高,以及 IL-6 和 TNF-α 等多种因子,促进了多种癌症类型的进展。
此外,Covid-19 的进展与 CD8+ 和 CD4+ T 细胞、B 细胞和NK 细胞数量的耗竭相关。总体而言,Covid-19 依赖的促炎特征和免疫抑制促进了肿瘤发生、恶性细胞的起始和免疫逃逸、肿瘤进展和转移以及癌症复发的最佳微环境。
然而,存在治疗机会窗口,可能同时对抗 Covid-19 和癌症,以改善患者预后。
The Covid-19 pandemic has spread rapidly across the globe, resulting in more than 3 million deaths worldwide. The symptoms of Covid-19 are usually mild and non-specific, however in some cases patients may develop acute respiratory distress syndrome (ARDS) and systemic inflammation.
Individuals with inflammatory or immunocompromising illnesses, such as cancer, are more susceptible to develop ARDS and have higher rates of mortality. This is mediated through an initial hyperstimulated immune response which results in elevated levels of pro-inflammatory cytokines and a subsequent cytokine storm. This potentiates positive feedback loops which are unable to be balanced by anti-inflammatory mediators.
Therefore, elevated levels of IL-1β, as a result of NLRP3 inflammasome activation, as well as IL-6 and TNF-α amongst many others, contribute to the progression of various cancer types.
Furthermore, Covid-19 progression is associated with the depletion of CD8 + and CD4 + T cells, B cell and natural killer cell numbers. Collectively, a Covid-19-dependent pro-inflammatory profile and immune suppression promotes the optimal microenvironment for tumourigenesis, initiation and immune evasion of malignant cells, tumour progression and metastasis as well as cancer recurrence. There are, however, therapeutic windows of opportunity that may combat both Covid-19 and cancer to improve patient outcomes.
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