Department of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates.
Int J Mol Sci. 2023 Aug 26;24(17):13269. doi: 10.3390/ijms241713269.
The role of neutrophils in breast cancer shows that the N1 proinflammatory subtype can suppress and attack the tumor. In contrast, the N2 pro-tumor subtype aids the tumor in its survival, progression, and metastasis. Recently, more focus has been directed to the role of innate myeloid cells, specifically neutrophils, in regulating the responses of lymphoid populations both in the progression of cancer and in response to therapy. However, the exact crosstalk between breast cancer cells and neutrophils is poorly understood. In this work, we used in-silico assays to investigate the role of the bidirectional effect of neutrophils on metastatic TNBC. Our reanalysis of publicly available data reveals that most TNBC's classified within the CE2 subtype are leukocyte-poor and have four major cell types in their ecotypes: dendritic cells, macrophages, fibroblasts, and epithelial cells. Further immune deconvolution of these patients revealed that a few cells significantly differed between groups, including macrophages, neutrophils, and T cells. All BC showed lower infiltrating neutrophils compared to healthy surrounding tissue. Treated TNBCs improved the count of infiltrating neutrophils in TNBC. Most TNBC patients have a unique CE2 ecotype, characterized by more basal-like epithelial cells, more neutrophils, and fewer mononuclear lymphocytes (B cells, macrophages M1, T cell CD4+ (non-regulatory), and T cell CD8+ and T regs). This can be related to our finding that CE2 TNBCs are characterized by a lower LCK and higher ERBB2, and their top DEGs are related to leukocyte activation and NFKB pathway.
中性粒细胞在乳腺癌中的作用表明，N1 促炎亚型可以抑制和攻击肿瘤。相比之下，N2 促肿瘤亚型有助于肿瘤的存活、进展和转移。最近，更多的注意力集中在固有髓样细胞（特别是中性粒细胞）在调节淋巴样细胞群对癌症进展和治疗反应的作用上。然而，乳腺癌细胞与中性粒细胞之间的确切串扰仍知之甚少。在这项工作中，我们使用了计算机模拟实验来研究中性粒细胞对转移性三阴性乳腺癌的双向作用的作用。我们对公开可用数据的重新分析表明，大多数被归类为 CE2 亚型的三阴性乳腺癌中白细胞较少，其生态型中有四种主要细胞类型：树突状细胞、巨噬细胞、成纤维细胞和上皮细胞。对这些患者的进一步免疫分解表明，少数细胞在组间有显著差异，包括巨噬细胞、中性粒细胞和 T 细胞。所有 BC 显示浸润性中性粒细胞均低于健康周围组织。治疗后的三阴性乳腺癌改善了三阴性乳腺癌中浸润性中性粒细胞的计数。大多数三阴性乳腺癌患者具有独特的 CE2 生态型，其特征是基底样上皮细胞更多，中性粒细胞更多，单核淋巴细胞（B 细胞、巨噬细胞 M1、T 细胞 CD4+（非调节性）和 T 细胞 CD8+和 Tregs）更少。这可能与我们的发现有关，即 CE2 三阴性乳腺癌的特征是 LCK 较低，ERBB2 较高，其顶级 DEGs 与白细胞激活和 NFKB 途径有关。
