Kiss Máté, Caro Aarushi Audhut, Raes Geert, Laoui Damya
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Front Oncol. 2020 Sep 17;10:1399. doi: 10.3389/fonc.2020.01399. eCollection 2020.
Monocytes influence multiple aspects of tumor progression, including antitumor immunity, angiogenesis, and metastasis, primarily by infiltrating tumors, and differentiating into tumor-associated macrophages. Emerging evidence suggests that the tumor-induced systemic environment influences the development and phenotype of monocytes before their arrival to the tumor site. As a result, circulating monocytes show functional alterations in cancer, such as the acquisition of immunosuppressive activity and reduced responsiveness to inflammatory stimuli. In this review, we summarize available evidence about cancer-induced changes in monopoiesis and its impact on the abundance and function of monocytes in the periphery. In addition, we describe the phenotypical alterations observed in tumor-educated peripheral blood monocytes and highlight crucial gaps in our knowledge about additional cellular functions that may be affected based on transcriptomic studies. We also highlight emerging therapeutic strategies that aim to reverse cancer-induced changes in monopoiesis and peripheral monocytes to inhibit tumor progression and improve therapy responses. Overall, we suggest that an in-depth understanding of systemic monocyte reprogramming will have implications for cancer immunotherapy and the development of clinical biomarkers.
单核细胞主要通过浸润肿瘤并分化为肿瘤相关巨噬细胞，影响肿瘤进展的多个方面，包括抗肿瘤免疫、血管生成和转移。新出现的证据表明，肿瘤诱导的全身环境在单核细胞到达肿瘤部位之前就会影响其发育和表型。因此，循环单核细胞在癌症中表现出功能改变，如获得免疫抑制活性和对炎症刺激的反应性降低。在这篇综述中，我们总结了关于癌症诱导的单核细胞生成变化及其对外周血单核细胞丰度和功能影响的现有证据。此外，我们描述了在肿瘤驯化的外周血单核细胞中观察到的表型改变，并强调了基于转录组学研究，我们在可能受影响的其他细胞功能方面的关键知识空白。我们还强调了旨在逆转癌症诱导的单核细胞生成和外周血单核细胞变化以抑制肿瘤进展并改善治疗反应的新兴治疗策略。总体而言，我们认为深入了解全身单核细胞重编程将对癌症免疫治疗和临床生物标志物的开发产生影响。
