Division of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Medical Scientist Training Program, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Bioessays. 2021 Jul;43(7):e2100029. doi: 10.1002/bies.202100029. Epub 2021 May 16.
Tumor necrosis is a common histological feature and poor prognostic predictor in various cancers. Despite its significant clinical implications, the mechanism underlying tumor necrosis remains largely unclear due to lack of appropriate pre-clinical modeling. We propose that tumor necrosis is a synergistic consequence of metabolic stress and inflammation, which lead to oxidative stress-induced cell death, such as ferroptosis. As a natural consequence of tumor expansion, tumor cells are inevitably stripped of vascular supply, resulting in deprivation of oxygen and nutrients. The resulting metabolic stress has commonly been considered the cause of tumor necrosis. Recent studies found that immune cells, such as neutrophils, when recruited to tumors, can directly trigger ferroptosis in tumor cells, suggesting that immune cells can be involved in amplifying tumor necrosis. This article will discuss potential mechanisms underlying tumor necrosis development and its impact on tumor progression as well as the immune response to tumors.
肿瘤坏死是各种癌症的一种常见组织学特征和预后不良的预测指标。尽管其具有重要的临床意义，但由于缺乏适当的临床前模型，肿瘤坏死的机制在很大程度上仍不清楚。我们提出，肿瘤坏死是代谢应激和炎症的协同后果，导致氧化应激诱导的细胞死亡，如铁死亡。由于肿瘤的扩张是不可避免的，肿瘤细胞会不可避免地失去血管供应，导致氧气和营养物质的剥夺。由此产生的代谢应激通常被认为是肿瘤坏死的原因。最近的研究发现，当免疫细胞（如中性粒细胞）被招募到肿瘤中时，它们可以直接触发肿瘤细胞中的铁死亡，这表明免疫细胞可以参与放大肿瘤坏死。本文将讨论肿瘤坏死发展的潜在机制及其对肿瘤进展和肿瘤免疫反应的影响。
