Kazakova Elena, Iamshchikov Pavel, Larionova Irina, Kzhyshkowska Julia
Laboratory of translational cellular and molecular biomedicine, National Research Tomsk State University, Tomsk, Russia.
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Front Oncol. 2023 Jan 6;12:1096897. doi: 10.3389/fonc.2022.1096897. eCollection 2022.
Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells that constitute up to 50% of the cell mass of human tumors. TAMs interact with the components of the tumor microenvironment (TME) by using scavenger receptors (SRs), a large superfamily of multifunctional receptors that recognize, internalize and transport to the endosomal/lysosomal pathway apoptotic cells, cytokines, matrix molecules, lipid modified lipoproteins and other unwanted-self ligands. In our review, we summarized state-of-the art for the role of macrophage scavenger receptors in tumor development and their significance as cancer biomarkers. In this review we focused on functional activity of TAM-expressing SRs in animal models and in patients, and summarized the data for different human cancer types about the prognostic significance of TAM-expressed SRs. We discussed the role of SRs in the regulation of cancer cell biology, cell-cell and cell-matrix interaction in TME, immune status in TME, angiogenesis, and intratumoral metabolism. Targeting of tumor-promoting SRs can be a promising therapeutic approach in anti-cancer therapy. In our review we provide evidence for both tumor supporting and tumor inhibiting functions of scavenger receptors expressed on TAMs. We focused on the key differences in the prognostic and functional roles of SRs that are specific for cancer types. We highlighted perspectives for inhibition of tumor-promoting SRs in anti-cancer therapy.
肿瘤相关巨噬细胞（TAM）是一类异质性髓样细胞群体，在人类肿瘤的细胞组成中占比高达50%。TAM通过清道夫受体（SR）与肿瘤微环境（TME）的成分相互作用，SR是一个多功能受体的大家族，可识别、内化并将凋亡细胞、细胞因子、基质分子、脂质修饰脂蛋白及其他有害的自身配体转运至内体/溶酶体途径。在我们的综述中，我们总结了巨噬细胞清道夫受体在肿瘤发展中的作用及其作为癌症生物标志物的意义。在本综述中，我们重点关注了在动物模型和患者中表达SR的TAM的功能活性，并总结了不同人类癌症类型中TAM表达的SR的预后意义的数据。我们讨论了SR在调节癌细胞生物学、TME中的细胞-细胞和细胞-基质相互作用、TME中的免疫状态、血管生成及肿瘤内代谢方面的作用。靶向促进肿瘤生长的SR可能是抗癌治疗中一种有前景的治疗方法。在我们的综述中，我们提供了TAM上表达的清道夫受体具有肿瘤支持和肿瘤抑制功能的证据。我们重点关注了特定癌症类型中SR在预后和功能作用方面的关键差异。我们强调了在抗癌治疗中抑制促进肿瘤生长的SR的前景。
