Division of Cell and Developmental Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
Methods Mol Biol. 2020;2115:289-325. doi: 10.1007/978-1-0716-0290-4_17.
Tumor-associated macrophages (TAMs) are representing a major leukocyte population in solid tumors. Macrophages are very heterogeneous and plastic cells and can acquire distinct functional phenotypes ranging from antitumorigenic to immunosuppressive tumor-promoting M2-like TAMs, depending on the local tissue microenvironment (TME). TAMs express cytokines, chemokines, growth factors, and extracellular matrix (ECM) modifying factors, and the cross talk with the TME regulates pathways involved in the recruitment, polarization, and metabolism of TAMs during tumor progression. Due to their crucial role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer with therapeutic agents that promote phagocytosis or suppress survival, proliferation, trafficking, or polarization of TAMs may prove to be beneficial in cancer therapy. In this chapter, we will discuss TAM biology and current strategies for the targeting of TAMs using small interfering RNA (siRNA)-based drugs. In the past few years, advances in the field of nanomedicine pave the way for the development of siRNA-based drugs as an additional class of personalized cancer immuno-nanomedicines. Fundamental challenges associated with this group of therapeutics include the development process, delivery system, and clinical translation for siRNA-based drugs.
肿瘤相关巨噬细胞（TAMs）是实体瘤中主要的白细胞群体之一。巨噬细胞具有很强的异质性和可塑性，可以根据局部组织微环境（TME）获得不同的功能表型，从抗肿瘤的到免疫抑制的肿瘤促进型 M2 样 TAMs。TAMs 表达细胞因子、趋化因子、生长因子和细胞外基质（ECM）修饰因子，与 TME 的相互作用调节了招募、极化和代谢 TAMs 的途径，这些途径参与肿瘤的进展。由于它们在肿瘤生长和转移中的关键作用，选择性地针对 TAM 治疗癌症，使用促进吞噬或抑制 TAMs 存活、增殖、迁移或极化的治疗剂，可能在癌症治疗中证明是有益的。在这一章中，我们将讨论 TAM 生物学和使用基于小干扰 RNA（siRNA）的药物靶向 TAMs 的当前策略。在过去的几年中，纳米医学领域的进展为基于 siRNA 的药物作为一类新的个性化癌症免疫纳米药物的发展铺平了道路。该类治疗药物的相关的主要挑战包括药物开发过程、递送系统和临床转化。
