Department of Biomedical Engineering, Pennsylvania State University, University Park, State College, PA, USA.
Adv Exp Med Biol. 2018;1092:113-138. doi: 10.1007/978-3-319-95294-9_7.
For the last three decades, the concept of immunoediting has evolved to characterize our increasing understanding of the interactions between cells from the immune system and cancer development. Elucidating the role of immune cells in the progression of cancer has been very challenging due to their dual role; the immune system can either suppress tumor formation by killing cancer cells, or it can also promote tumor growth. Revealing how immune cells are hampered by the tumor microenvironment and how they aid tumor progression has signaled strategies to reverse these effects and control cancer cell growth; this has been the advent of immunotherapy design. More recently, the role of physical forces in the process of immunoediting has been highlighted by multiple studies focusing on understanding how force changes in the stiffness of the extracellular matrix and fluid flow shear stress contribute to tumor development. Using models in vitro that incorporate biomechanical components, it has been shown that these physical aspects are not only important during the formation and growth of primary tumors, but in the metastatic process as well. In this way, we have also gained insight into the interactions occurring within the vascular system, which are highly affected by the dynamics of physical collisions between cells and by shear forces. Here, we review the concept of cancer immunoediting with an emphasis on biomechanics and conclude with a summary on current immunotherapies and potential new strategies.
在过去的三十年中,免疫编辑的概念不断发展,使我们对免疫系统细胞与癌症发展之间的相互作用的认识不断加深。由于免疫细胞具有双重作用——既可以通过杀死癌细胞来抑制肿瘤的形成,也可以促进肿瘤的生长,因此阐明免疫细胞在癌症进展中的作用极具挑战性。揭示免疫细胞如何受到肿瘤微环境的阻碍以及它们如何促进肿瘤进展,为逆转这些效应和控制癌细胞生长提供了策略;这就是免疫疗法设计的出现。最近,多项研究强调了物理力在免疫编辑过程中的作用,这些研究专注于了解细胞间的力变化如何改变细胞外基质的硬度和流体流动切应力,从而促进肿瘤的发展。通过使用整合生物力学组件的体外模型,已经表明这些物理因素不仅在原发性肿瘤的形成和生长过程中很重要,而且在转移过程中也是如此。通过这种方式,我们还深入了解了血管系统内发生的相互作用,这些相互作用受到细胞间物理碰撞和切应力的动力学的强烈影响。在这里,我们重点介绍了癌症免疫编辑的概念,并对生物力学进行了总结,最后对当前的免疫疗法和潜在的新策略进行了总结。