Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital, Sygehusvej 10, 4000 Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark; Department of Surgical Pathology, Zealand University Hospital, Sygehusvej 9, 4000 Roskilde, Denmark.
Clin Immunol. 2021 Nov;232:108847. doi: 10.1016/j.clim.2021.108847. Epub 2021 Sep 27.
Cancer development is among other factors driven by tumor immune escape and tumor-mediated changes in the immune response. Investigating systemic immune changes may provide important knowledge for the improvement of patient prognosis and treatment opportunities.
The systemic immune profile of patients with ER-positive breast cancer (n = 22) and healthy controls (n = 30) was investigated based on complete blood counts, flow cytometric analysis of T cell subsets including regulatory T cells (Tregs), and immune assays investigating soluble (s)HLA-G and the cytokine profile in plasma. We further examined the correlation between the immune markers and clinical parameters including tumor size, tumor grade and lymph node involvement.
Results indicated that breast cancer patients possessed a higher amount of neutrophils and monocytes and fewer lymphocytes and eosinophils compared with healthy controls. Breast cancer patients had significantly more CD25CD127 Tregs than controls, and both lymphocyte and Treg numbers were negatively correlated with tumor size. Furthermore, Treg numbers were elevated in grade I tumors compared with grade II tumors and with healthy controls. No difference in sHLA-G levels was observed between patients and controls. Higher levels of IL-6 and TNF-α were observed in breast cancer patients. Cytokine and sHLA-G levels were not associated with clinical parameters.
The results of this exploratory study contribute to the elucidation of the systemic immune response in breast cancer indicating a potential use of peripheral immune cell counts and Tregs to distinguish patients from healthy controls and as potential diagnostic and prognostic biomarkers to be investigated in future studies.
肿瘤免疫逃逸和肿瘤介导的免疫反应改变等因素驱动癌症发展。研究系统性免疫变化可能为改善患者预后和治疗机会提供重要知识。
基于全血细胞计数、包括调节性 T 细胞 (Tregs) 在内的 T 细胞亚群的流式细胞术分析以及对血浆中可溶性 (s)HLA-G 和细胞因子谱的免疫检测，研究了 ER 阳性乳腺癌患者 (n=22) 和健康对照者 (n=30) 的系统性免疫特征。我们进一步检查了免疫标志物与包括肿瘤大小、肿瘤分级和淋巴结受累在内的临床参数之间的相关性。
结果表明，与健康对照组相比，乳腺癌患者具有更多的中性粒细胞和单核细胞，更少的淋巴细胞和嗜酸性粒细胞。乳腺癌患者的 CD25CD127 Tregs 明显多于对照组，并且淋巴细胞和 Treg 数量与肿瘤大小呈负相关。此外，I 级肿瘤的 Treg 数量高于 II 级肿瘤和健康对照组。患者和对照组之间的 sHLA-G 水平没有差异。乳腺癌患者的 IL-6 和 TNF-α 水平较高。细胞因子和 sHLA-G 水平与临床参数无关。
这项探索性研究的结果有助于阐明乳腺癌中的系统性免疫反应，表明外周免疫细胞计数和 Tregs 具有潜在用途，可用于区分患者和健康对照者，以及作为未来研究中有待调查的潜在诊断和预后生物标志物。
