Kruk Linus, Mamtimin Medina, Braun Attila, Anders Hans-Joachim, Andrassy Joachim, Gudermann Thomas, Mammadova-Bach Elmina
Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilian-University, 80336 Munich, Germany.
Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig-Maximilian-University, 80336 Munich, Germany.
Cancers (Basel). 2023 Apr 9;15(8):2212. doi: 10.3390/cancers15082212.
Cancer-associated inflammation has been established as a hallmark feature of almost all solid cancers. Tumor-extrinsic and intrinsic signaling pathways regulate the process of cancer-associated inflammation. Tumor-extrinsic inflammation is triggered by many factors, including infection, obesity, autoimmune disorders, and exposure to toxic and radioactive substances. Intrinsic inflammation can be induced by genomic mutation, genome instability and epigenetic remodeling in cancer cells that promote immunosuppressive traits, inducing the recruitment and activation of inflammatory immune cells. In RCC, many cancer cell-intrinsic alterations are assembled, upregulating inflammatory pathways, which enhance chemokine release and neoantigen expression. Furthermore, immune cells activate the endothelium and induce metabolic shifts, thereby amplifying both the paracrine and autocrine inflammatory loops to promote RCC tumor growth and progression. Together with tumor-extrinsic inflammatory factors, tumor-intrinsic signaling pathways trigger a Janus-faced tumor microenvironment, thereby simultaneously promoting or inhibiting tumor growth. For therapeutic success, it is important to understand the pathomechanisms of cancer-associated inflammation, which promote cancer progression. In this review, we describe the molecular mechanisms of cancer-associated inflammation that influence cancer and immune cell functions, thereby increasing tumor malignancy and anti-cancer resistance. We also discuss the potential of anti-inflammatory treatments, which may provide clinical benefits in RCCs and possible avenues for therapy and future research.
癌症相关炎症已被确认为几乎所有实体癌的一个标志性特征。肿瘤外在和内在信号通路调节癌症相关炎症的过程。肿瘤外在炎症由多种因素触发，包括感染、肥胖、自身免疫性疾病以及接触有毒和放射性物质。内在炎症可由癌细胞中的基因突变、基因组不稳定和表观遗传重塑诱导，这些因素促进免疫抑制特征，诱导炎性免疫细胞的募集和激活。在肾细胞癌（RCC）中，许多癌细胞内在改变聚集在一起，上调炎症通路，增强趋化因子释放和新抗原表达。此外，免疫细胞激活内皮细胞并诱导代谢转变，从而放大旁分泌和自分泌炎症循环，以促进RCC肿瘤的生长和进展。与肿瘤外在炎症因子一起，肿瘤内在信号通路触发一个双面的肿瘤微环境，从而同时促进或抑制肿瘤生长。为了治疗成功，了解促进癌症进展的癌症相关炎症的发病机制很重要。在这篇综述中，我们描述了影响癌症和免疫细胞功能的癌症相关炎症的分子机制，从而增加肿瘤恶性程度和抗癌抗性。我们还讨论了抗炎治疗的潜力，其可能为RCC提供临床益处以及治疗和未来研究的可能途径。
