Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, South Africa.
Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, South Africa.
Cytokine Growth Factor Rev. 2022 Feb;63:78-89. doi: 10.1016/j.cytogfr.2021.10.005. Epub 2021 Oct 23.
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.
Covid-19 疫情在全球迅速蔓延,导致全球超过 300 万人死亡。Covid-19 的症状通常较轻且非特异性,但在某些情况下,患者可能会发展为急性呼吸窘迫综合征(ARDS)和全身炎症。患有炎症或免疫功能低下疾病(如癌症)的个体更容易发生 ARDS,死亡率更高。这是通过初始过度激活的免疫反应介导的,导致促炎细胞因子水平升高和随后的细胞因子风暴。这增强了正反馈回路,而抗炎介质无法平衡这些回路。因此,NLRP3 炎性小体激活导致的 IL-1β 以及 IL-6 和 TNF-α 等多种细胞因子的水平升高,导致各种癌症类型的进展。此外,Covid-19 的进展与 CD8 和 CD4 T 细胞、B 细胞和自然杀伤细胞数量的减少有关。总之,Covid-19 依赖性促炎谱和免疫抑制促进了肿瘤发生、恶性细胞的免疫逃逸、肿瘤进展和转移以及癌症复发的最佳微环境。然而,存在一些治疗机会窗口,可能同时对抗 Covid-19 和癌症,以改善患者的预后。