iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal.
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
Int J Mol Sci. 2021 Feb 17;22(4):1972. doi: 10.3390/ijms22041972.
The immune microenvironment of breast cancer (BC) is composed by high macrophage infiltrates, correlated with the most aggressive subtypes. Tumour-associated macrophages (TAM) within the BC microenvironment are key regulators of immune suppression and BC progression. Nevertheless, several key questions regarding TAM polarisation by BC are still not fully understood. Recently, the modulation of the immune microenvironment has been described via the recognition of abnormal glycosylation patterns at BC cell surface. These patterns rise as a resource to identify potential targets on TAM in the BC context, leading to the development of novel immunotherapies. Herein, we will summarize recent studies describing advances in identifying altered glycan structures in BC cells. We will focus on BC-specific glycosylation patterns known to modulate the phenotype and function of macrophages recruited to the tumour site, such as structures with sialylated or N-acetylgalactosamine epitopes. Moreover, the lectins present at the surface of macrophages reported to bind to such antigens, inducing tumour-prone TAM phenotypes, will also be highlighted. Finally, we will discuss and give our view on the potential and current challenges of targeting these glycan-lectin interactions to reshape the immunosuppressive landscape of BC.
乳腺癌（BC）的免疫微环境由高巨噬细胞浸润组成，与侵袭性最强的亚型相关。BC 微环境中的肿瘤相关巨噬细胞（TAM）是免疫抑制和 BC 进展的关键调节剂。然而，关于 BC 对 TAM 极化的几个关键问题仍未完全阐明。最近，通过识别 BC 细胞表面异常糖基化模式，对免疫微环境的调节进行了描述。这些模式为在 BC 背景下识别 TAM 上的潜在靶标提供了资源，从而导致新的免疫疗法的发展。本文将总结最近描述鉴定 BC 细胞中改变的糖基结构的研究进展。我们将重点关注已知调节募集到肿瘤部位的巨噬细胞表型和功能的 BC 特异性糖基化模式，例如具有唾液酸化或 N-乙酰半乳糖胺表位的结构。此外，还将突出报道与这些抗原结合的存在于巨噬细胞表面的凝集素，诱导倾向于肿瘤的 TAM 表型。最后，我们将讨论并阐述针对这些糖-凝集素相互作用的潜力和当前挑战，以重塑 BC 的免疫抑制景观。
