Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Breast Cancer Res Treat. 2021 Jan;185(2):261-279. doi: 10.1007/s10549-020-05954-2. Epub 2020 Oct 3.
Ductal breast carcinoma as a heterogeneous disease has different molecular subtypes associated with clinical prognosis and patients' survival. The role of immune system as a consistent part of the tumor microenvironment (TME) has been documented in progression of ductal breast carcinoma. Here, we aimed to describe the important immune cells and the immune system-associated molecules in Ductal Carcinoma In situ (DCIS) and Invasive Ductal Carcinoma (IDC) with special emphasis on their associations with different molecular subtypes and patients' prognosis.
The immune cells have a dual role in breast cancer (BC) microenvironment depending on the molecular subtype or tumor grade. These cells with different frequencies are present in the TME of DCIS and IDC. The presence of regulatory cells including Tregs, MDSC, Th2, Th17, M2 macrophages, HLADR T cells, and Tγδ cells is related to more immunosuppressive microenvironment, especially in ER and TN subtypes. In contrast, NK cells, CTL, Th, and Tfh cells are associated to the anti-tumor activity. These cells are higher in ER BC, although in other subtypes such as TN or HER2 are associated with a favorable prognosis.
Determining the specific immune response in each subtype could be helpful in estimating the possible behavior of the tumor cells in TME. It is important to realize that different frequencies of immune cells in BC environment likely determine the patients' prognosis and their survival in each subtype. Therefore, elucidation of the distinct immune players in TME would be helpful toward developing targeted therapies in each subtype.
作为一种异质性疾病，导管乳腺癌具有不同的分子亚型，与临床预后和患者生存相关。免疫系统作为肿瘤微环境（TME）的固有组成部分，在导管乳腺癌的进展中发挥着重要作用。在此，我们旨在描述导管原位癌（DCIS）和浸润性导管癌（IDC）中重要的免疫细胞和与免疫系统相关的分子，特别强调它们与不同分子亚型和患者预后的关联。
免疫细胞在乳腺癌（BC）微环境中具有双重作用，取决于分子亚型或肿瘤分级。这些具有不同频率的细胞存在于 DCIS 和 IDC 的 TME 中。调节性细胞（包括 Tregs、MDSC、Th2、Th17、M2 巨噬细胞、HLADR T 细胞和 Tγδ 细胞）的存在与更具免疫抑制性的微环境相关，特别是在 ER 和 TN 亚型中。相比之下，NK 细胞、CTL、Th 和 Tfh 细胞与抗肿瘤活性相关。这些细胞在 ERBC 中更为常见，尽管在其他亚型如 TN 或 HER2 中与预后良好相关。
确定每个亚型中特定的免疫反应有助于估计肿瘤细胞在 TME 中的可能行为。重要的是要认识到，BC 环境中免疫细胞的不同频率可能决定了患者在每个亚型中的预后和生存。因此，阐明 TME 中的不同免疫参与者将有助于为每个亚型开发靶向治疗。
