Laboratory of Tumor Microenvironment and Therapeutic Resistance, Department of Oncology, VIB-Center for Cancer Biology, KU Leuven, Leuven, Belgium.
Department of Neurological Surgery, UCSF Comprehensive Cancer Center, UCSF, San Francisco, CA, United States.
Front Immunol. 2019 Sep 12;10:2178. doi: 10.3389/fimmu.2019.02178. eCollection 2019.
The wound repair program is tightly regulated and coordinated among different cell constituents including epithelial cells, fibroblasts, immune cells and endothelial cells following consecutive steps to ensure timely, and proper wound closure. Specifically, innate and adaptive immune cells are pivotal participants that also closely interact with the vasculature. Tumors are portrayed as wounds that do not heal because they undergo continuous stromal remodeling and vascular growth with immunosuppressive features to ensure tumor propagation; a stage that is reminiscent of the proliferative resolution phase in wound repair. There is increasing evidence from mouse model systems and clinical trials that targeting both the immune and vascular compartments is an attractive therapeutic approach to reawaken the inflammatory status in the "tumor wound" with the final goal to abrogate tumor cells and invigorate tissue homeostasis. In this review, we compare the implication of immune cells and the vasculature in chronic wounds and tumor wounds to underscore the conceptual idea of transitioning tumors into an inflammatory wound-like state with antiangiogenic immunotherapies to improve beneficial effects in cancer patients.
伤口修复程序在不同的细胞成分(包括上皮细胞、成纤维细胞、免疫细胞和内皮细胞)之间受到严格的调控和协调,包括连续的步骤,以确保及时、适当的伤口闭合。具体来说,先天和适应性免疫细胞是关键的参与者,它们也与血管密切相互作用。肿瘤被描绘为不会愈合的伤口,因为它们经历持续的基质重塑和血管生长,具有免疫抑制特征,以确保肿瘤的传播;这一阶段让人联想到伤口修复中的增殖消退阶段。越来越多的来自小鼠模型系统和临床试验的证据表明,靶向免疫和血管两个方面是一种有吸引力的治疗方法,可以重新激活“肿瘤伤口”中的炎症状态,最终目的是消除肿瘤细胞并激活组织稳态。在这篇综述中,我们比较了免疫细胞和血管在慢性伤口和肿瘤伤口中的作用,以强调将肿瘤转变为炎症性伤口样状态的概念,用抗血管生成免疫疗法来提高癌症患者的治疗效果。