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超越免疫抑制:促肿瘤髓系细胞在乳腺癌中的多面功能

Beyond Immunosuppression: The Multifaceted Functions of Tumor-Promoting Myeloid Cells in Breast Cancers.

作者信息

Blaye Céline, Boyer Thomas, Peyraud Florent, Domblides Charlotte, Larmonier Nicolas

机构信息

Centre National de la Recherche Scientific (CNRS) Unité Mixte de Recherche (UMR) 5164, ImmunoConcEpT, Bordeaux, France.

Department of Medical Oncology, Institut Bergonié, Bordeaux, France.

出版信息

Front Immunol. 2022 Mar 3;13:838040. doi: 10.3389/fimmu.2022.838040. eCollection 2022.

Abstract

Breast cancers are commonly associated with an immunosuppressive microenvironment responsible for tumor escape from anti-cancer immunity. Cells of the myeloid lineage account for a major part of this tumor-promoting landscape. These myeloid cells are composed of heterogeneous subsets at different stages of differentiation and have traditionally been described by their cardinal ability to suppress innate and adaptive anticancer immunity. However, evidence has accumulated that, beyond their immunosuppressive properties, breast cancer-induced myeloid cells are also equipped with a broad array of "non-immunological" tumor-promoting functions. They therefore represent major impediments for anticancer therapies, particularly for immune-based interventions. We herein analyze and discuss current literature related to the versatile properties of the different myeloid cell subsets engaged in breast cancer development. We critically assess persisting difficulties and challenges in unequivocally discriminate dedicated subsets, which has so far prevented both the selective targeting of these immunosuppressive cells and their use as potential biomarkers. In this context, we propose the concept of IMCGL, "pro-tumoral immunosuppressive myeloid cells of the granulocytic lineage", to more accurately reflect the contentious nature and origin of granulocytic cells in the breast tumor microenvironment. Future research prospects related to the role of this myeloid landscape in breast cancer are further considered.

摘要

乳腺癌通常与免疫抑制性微环境相关,这种微环境导致肿瘤逃避免疫抗癌作用。髓系细胞在这种促进肿瘤生长的环境中占主要部分。这些髓系细胞由处于不同分化阶段的异质亚群组成,传统上根据其抑制先天性和适应性抗癌免疫的主要能力来描述。然而,越来越多的证据表明,除了其免疫抑制特性外,乳腺癌诱导的髓系细胞还具有广泛的“非免疫性”促进肿瘤生长的功能。因此,它们是抗癌治疗的主要障碍,尤其是基于免疫的干预措施。我们在此分析和讨论与参与乳腺癌发展的不同髓系细胞亚群的多功能特性相关的当前文献。我们批判性地评估了在明确区分特定亚群方面仍然存在的困难和挑战,这迄今为止既阻碍了对这些免疫抑制细胞的选择性靶向,也阻碍了它们作为潜在生物标志物的应用。在此背景下,我们提出了IMCGL的概念,即“粒细胞系促肿瘤免疫抑制性髓系细胞”,以更准确地反映乳腺肿瘤微环境中粒细胞的争议性质和来源。进一步考虑了与这种髓系环境在乳腺癌中的作用相关的未来研究前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fad/8927658/8a68b6cc9d2f/fimmu-13-838040-g001.jpg

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