Singapore-MIT Alliance for Research and Technology (SMART), BioSystems and Micromechanics (BioSyM) IRG, Singapore, Singapore.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Adv Exp Med Biol. 2020;1224:87-115. doi: 10.1007/978-3-030-35723-8_7.
Monocytes (Mos) are immune cells that critically regulate cancer, enabling tumor growth and modulating metastasis. Mos can give rise to tumor-associated macrophages (TAMs) and Mo-derived dendritic cells (moDCs), all of which shape the tumor microenvironment (TME). Thus, understanding their roles in the TME is key for improved immunotherapy. Concurrently, various biological and mechanical factors including changes in local cytokines, extracellular matrix production, and metabolic changes in the TME affect the roles of monocytic cells. As such, relevant TME models are critical to achieve meaningful insight on the precise functions, mechanisms, and effects of monocytic cells. Notably, murine models have yielded significant insight into human Mo biology. However, many of these results have yet to be confirmed in humans, reinforcing the need for improved in vitro human TME models for the development of cancer interventions. Thus, this chapter (1) summarizes current insight on the tumor biology of Mos, TAMs, and moDCs, (2) highlights key therapeutic applications relevant to these cells, and (3) discusses various TME models to study their TME-related activity. We conclude with a perspective on the future research trajectory of this topic.
单核细胞（Mos）是免疫细胞，它们对癌症具有关键的调控作用，能够促进肿瘤生长并调节转移。Mos 可以分化为肿瘤相关巨噬细胞（TAMs）和 Mo 来源的树突状细胞（moDCs），所有这些细胞都能塑造肿瘤微环境（TME）。因此，了解它们在 TME 中的作用对于改善免疫治疗至关重要。同时，各种生物和机械因素，包括局部细胞因子的变化、细胞外基质的产生以及 TME 中的代谢变化，都会影响单核细胞的作用。因此，相关的 TME 模型对于深入了解单核细胞的精确功能、机制和影响至关重要。值得注意的是，鼠模型为人类 Mo 生物学提供了重要的见解。然而，其中许多结果尚未在人类中得到证实，这进一步强调了需要改进体外人类 TME 模型以开发癌症干预措施。因此，本章（1）总结了当前关于 Mos、TAMs 和 moDCs 的肿瘤生物学的研究进展，（2）强调了与这些细胞相关的关键治疗应用，（3）讨论了各种 TME 模型，以研究它们与 TME 相关的活性。最后，我们对该主题的未来研究方向进行了展望。
