Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India.
AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, Andhra Pradesh, India.
Curr Med Chem. 2021;28(39):8203-8236. doi: 10.2174/0929867328666210720143721.
Tumor associated macrophages (TAMs), located in the tumor microenvironment (TME), play a significant role in cancer cell survival and progression. TAMs have been involved in producing immuno-suppressive TME in the tumor by generating inflammatory mediators, growth factors, cytokines, chemokines, etc. TAMs can influence the angiogenesis, metastatic behavior of tumor cells (TCs) and cause multidrug resistance. TAMs within the TME can enhance cancer cell metastasis and are stromal and perivascular. The angiogenesis is promoted at the hypoxia, and the avascular zones of TME. Differentiation states of TAMs are considered 'plastic' as they exhibit temporal expression of one or several phenotypes depending on local cues. Emerging cancer research depicted the epigenetic regulation of macrophage polarization (both M1s, M2s) and their potential implications to develop pharmacologic modulators and microRNAs to act as molecular switches and even to serve as targeted therapies to inhibit tumor growth. In the present article, the role of TAMs in tumor progression, angiogenesis and metastasis was discussed. In addition, key signaling cascades regulated by TAMs, which have a role in chemoresistance, were also discussed. Currently, novel pleiotropic properties of various anticancer phytomedicines are gaining importance as they assist in overcoming TAMs-induced chemoresistance. Moreover, these phytomedicines are being tested as 'adjunct therapeutics' along with chemotherapeutic agents, anti-angiogenic molecules, anti-metastatic compounds, and other immune-checkpoint blockers against tumor metastasis/angiogenesis. Hence, a brief note on natural products targeting TAMs was provided. In summary, this review would benefit pharmacologists and medical professionals to develop therapies to target TAMs using multi-OMICs approaches, including genomics, epigenomics, transcriptomics, and proteomics.
肿瘤相关巨噬细胞（TAMs）位于肿瘤微环境（TME）中，在癌细胞存活和进展中发挥重要作用。TAMs 通过产生炎症介质、生长因子、细胞因子、趋化因子等，参与产生肿瘤中的免疫抑制性 TME。TAMs 可以影响血管生成、肿瘤细胞（TCs）的转移行为，并导致多药耐药。TME 中的 TAMs 可以增强癌细胞的转移，并促进肿瘤间质和血管周围的转移。血管生成在 TME 的缺氧和无血管区得到促进。TAMs 的分化状态被认为是“可塑性的”，因为它们根据局部线索表现出一种或几种表型的暂时表达。新兴的癌症研究描述了巨噬细胞极化（M1、M2）的表观遗传调控及其潜在意义，即开发药理调节剂和 microRNAs 作为分子开关，甚至作为靶向治疗来抑制肿瘤生长。在本文中，讨论了 TAMs 在肿瘤进展、血管生成和转移中的作用。此外，还讨论了 TAMs 调节的关键信号级联反应，这些信号级联反应在化疗耐药中起作用。目前，各种抗癌植物药的多种多效性特性正变得越来越重要，因为它们有助于克服 TAMs 诱导的化疗耐药性。此外，这些植物药正在与化疗药物、抗血管生成分子、抗转移化合物和其他免疫检查点抑制剂一起作为“辅助治疗”进行测试，以对抗肿瘤转移/血管生成。因此，提供了关于针对 TAMs 的天然产物的简要说明。总之，这篇综述将使药理学家和医疗专业人员受益，他们可以使用多组学方法（包括基因组学、表观基因组学、转录组学和蛋白质组学）开发针对 TAMs 的治疗方法。
