Du Wenxuan, Nair Praful, Johnston Adrian, Wu Pei-Hsun, Wirtz Denis
Institute for NanoBiotechnology, Department of Chemical and Biomolecular Engineering, and Johns Hopkins Physical Sciences Oncology Center, Johns Hopkins University, Baltimore, Maryland, USA; email:
Department of Oncology, Department of Pathology, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Annu Rev Biomed Eng. 2022 Jun 6;24:275-305. doi: 10.1146/annurev-bioeng-110320-110749. Epub 2022 Apr 6.
Migration is an essential cellular process that regulates human organ development and homeostasis as well as disease initiation and progression. In cancer, immune and tumor cell migration is strongly associated with immune cell infiltration, immune escape, and tumor cell metastasis, which ultimately account for more than 90% of cancer deaths. The biophysics and molecular regulation of the migration of cancer and immune cells have been extensively studied separately. However, accumulating evidence indicates that, in the tumor microenvironment, the motilities of immune and cancer cells are highly interdependent via secreted factors such as cytokines and chemokines. Tumor and immune cells constantly express these soluble factors, which produce a tightly intertwined regulatory network for these cells' respective migration. A mechanistic understanding of the reciprocal regulation of soluble factor-mediated cell migration can provide critical information for the development of new biomarkers of tumor progression and of tumor response to immuno-oncological treatments. We review the biophysical andbiomolecular basis for the migration of immune and tumor cells and their associated reciprocal regulatory network. We also describe ongoing attempts to translate this knowledge into the clinic.
细胞迁移是一种重要的细胞过程，它调节人体器官的发育与稳态，以及疾病的起始和进展。在癌症中，免疫细胞和肿瘤细胞的迁移与免疫细胞浸润、免疫逃逸及肿瘤细胞转移密切相关，而这些最终导致了超过90%的癌症死亡。癌症细胞和免疫细胞迁移的生物物理学及分子调控已分别得到广泛研究。然而，越来越多的证据表明，在肿瘤微环境中，免疫细胞和癌细胞的运动性通过细胞因子和趋化因子等分泌因子高度相互依赖。肿瘤细胞和免疫细胞持续表达这些可溶性因子，这些因子为这些细胞各自的迁移产生了一个紧密交织的调控网络。对可溶性因子介导的细胞迁移的相互调控的机制性理解可为肿瘤进展新生物标志物以及肿瘤对免疫肿瘤治疗反应的开发提供关键信息。我们综述了免疫细胞和肿瘤细胞迁移的生物物理学和生物分子基础及其相关的相互调控网络。我们还描述了将这一知识转化到临床的正在进行的尝试。
