Vaught David B, Stanford Jamie C, Cook Rebecca S
Department of Cancer Biology, Vanderbilt University, Nashville, TN, 37232 USA.
Department of Breast Cancer Research Program Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, 37232 USA.
Cancer Cell Microenviron. 2015;2(1). doi: 10.14800/ccm.666.
Programmed cell death, or apoptosis, occurs in nearly all tissues of all multi-cellular organisms. In order to avoid leakage of intracellular contents, which could generate tissue damaging inflammation, apoptotic cells are cleared from tissues by phagocytes, which then dispatch the engulfed dying cell through the lysosomal pathway. Phagocytic clearance of apoptotic cells is referred to as efferocytosis. One key feature of efferocytosis is the production and release of wound healing cytokines by the phagocyte, which acts to resolve inflammation, and promote tissue repair. Phagocytic engulfment of apoptotic cells coupled with cytokine modulation aimed at immune suppression ensures that physiological programmed cell death does not induce inflammation and tissue damage. However, cytokines involved in wound healing and immune suppression are notorious for their role in the tumor microenvironment, increasing tumor cell motility and promoting evasion of anti-tumor immunity. Therefore, current and future studies aimed at targeting important players of efferocytosis should reveal new and efficacious therapeutic approaches for limiting cancer progression and relapse.
程序性细胞死亡,即细胞凋亡,几乎发生在所有多细胞生物的所有组织中。为了避免细胞内物质泄漏,因为这可能引发组织损伤性炎症,凋亡细胞会被吞噬细胞从组织中清除,吞噬细胞随后通过溶酶体途径处理被吞噬的垂死细胞。凋亡细胞的吞噬清除被称为胞葬作用。胞葬作用的一个关键特征是吞噬细胞产生并释放促进伤口愈合的细胞因子,这些细胞因子可起到消除炎症、促进组织修复的作用。凋亡细胞的吞噬作用与旨在免疫抑制的细胞因子调节相结合,确保生理性程序性细胞死亡不会引发炎症和组织损伤。然而,参与伤口愈合和免疫抑制的细胞因子因其在肿瘤微环境中的作用而声名狼藉,它们会增加肿瘤细胞的运动性并促进肿瘤逃避抗肿瘤免疫。因此,目前和未来旨在针对胞葬作用重要参与者的研究应揭示限制癌症进展和复发的新的有效治疗方法。