Yang Elton, Chua Wei, Ng Weng, Roberts Tara Laurine
School of Medicine, Western Sydney University, Campbelltown 2560, Australia.
Ingham Institute for Applied Medical Research, Liverpool 2170, Australia.
Biomedicines. 2021 Dec 14;9(12):1916. doi: 10.3390/biomedicines9121916.
Although strong connections exist between the carcinogenesis of gastric cancer and chronic inflammation, gastric cancer is unique in that the chronic gastritis which frequently precedes carcinogenesis is strongly associated with infection. The interplay between virulence factors and host immune cells is complex but culminates in the activation of inflammatory pathways and transcription factors such as NF-κB, STAT3, and AP-1, all of which upregulate cytokine production. Due to the key role of cytokines in modulating the immune response against tumour cells as well as possibly stimulating tumour growth and proliferation, different patterns of cytokine secretion may be associated with varying patient outcomes. In relation to gastric cancer, interleukin-6, 8, 10, 17A, TNF, and IFN-γ may have pro-tumour properties, although interleukin-10, TNF, and IFN-γ may have anti-tumour effects. However, due to the lack of studies investigating patient outcomes, only a link between higher interleukin-6 levels and poorer prognosis has been demonstrated. Further investigations which link peripheral cytokine levels to patient prognosis may elucidate important pathological mechanisms in gastric cancer which adversely impact patient survival and allow treatments targeting these processes to be developed.
尽管胃癌的致癌作用与慢性炎症之间存在紧密联系,但胃癌的独特之处在于,癌变之前常见的慢性胃炎与感染密切相关。毒力因子与宿主免疫细胞之间的相互作用很复杂,但最终会导致炎症途径和转录因子(如核因子κB、信号转导和转录激活因子3以及激活蛋白-1)的激活,所有这些都会上调细胞因子的产生。由于细胞因子在调节针对肿瘤细胞的免疫反应以及可能刺激肿瘤生长和增殖方面发挥关键作用,不同的细胞因子分泌模式可能与不同的患者预后相关。就胃癌而言,白细胞介素-6、8、10、17A、肿瘤坏死因子和干扰素-γ可能具有促肿瘤特性,尽管白细胞介素-10、肿瘤坏死因子和干扰素-γ可能具有抗肿瘤作用。然而,由于缺乏研究患者预后的相关研究,仅证实了白细胞介素-6水平升高与较差预后之间的联系。将外周血细胞因子水平与患者预后联系起来的进一步研究,可能会阐明胃癌中对患者生存产生不利影响的重要病理机制,并有助于开发针对这些过程的治疗方法。