Department of Immunology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Life Sci. 2020 Sep 15;257:118117. doi: 10.1016/j.lfs.2020.118117. Epub 2020 Jul 18.
B cells can promote or inhibit immune responses against breast cancer. We investigated changes in the frequency of B cells with stimulatory or regulatory capacity in breast tumor draining lymph nodes during cancer progression.
We isolated mononuclear cells from fresh axillary lymph nodes (LNs) of 44 patients with breast cancer and stained lymphocytes with antibodies against CD19, CD80, CD86, CD39 and CD73. To assess programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) expression, lymphocytes were briefly stimulated, stained for CD19, PD-1 and PD-L1, and examined with flow cytometry.
The frequency of CD80 B cells was higher in nonmetastatic lymph nodes, while the percentage of CD86 B cells showed a positive relationship with higher tumor grade and higher numbers of involved LNs. A small proportion of unstimulated B cells expressed PD-1 or PD-L1 but these molecules were rapidly upregulated on B cells following activation. The frequency of stimulated PD-L1 B cells showed an inverse association with estrogen and progesterone receptor expression and a nonsignificant positive association with tumor grade. In addition, the percentage of unstimulated PD-1 B cells was higher in patients with higher-grade tumors. CD73 expression on B cells was associated with lower numbers of involved LNs, and the frequency of CD39 B cells was higher in patients with larger tumors.
CD86, CD39, PD-1 and PD-L1 B cells showed associations with poor prognostic factors, therefore their potential role in the suppression of the immune responses against breast cancer should be evaluated in greater detail.
B 细胞可以促进或抑制针对乳腺癌的免疫反应。我们研究了在癌症进展过程中，乳腺肿瘤引流淋巴结中具有刺激或调节能力的 B 细胞频率的变化。
我们从 44 例乳腺癌患者新鲜腋窝淋巴结（LN）中分离单核细胞，并用针对 CD19、CD80、CD86、CD39 和 CD73 的抗体对淋巴细胞进行染色。为了评估程序性死亡-1（PD-1）和 PD-配体 1（PD-L1）的表达，将淋巴细胞短暂刺激，用 CD19、PD-1 和 PD-L1 染色，并通过流式细胞术进行检测。
非转移性淋巴结中 CD80 B 细胞的频率较高，而 CD86 B 细胞的百分比与较高的肿瘤分级和较多受累的淋巴结呈正相关。一小部分未刺激的 B 细胞表达 PD-1 或 PD-L1，但这些分子在 B 细胞激活后迅速上调。刺激的 PD-L1 B 细胞的频率与雌激素和孕激素受体的表达呈负相关，与肿瘤分级呈正相关，但无统计学意义。此外，高分级肿瘤患者中未刺激的 PD-1 B 细胞的百分比较高。B 细胞上的 CD73 表达与受累淋巴结数量较少有关，而 CD39 B 细胞的频率在肿瘤较大的患者中较高。
CD86、CD39、PD-1 和 PD-L1 B 细胞与不良预后因素有关，因此应更详细地评估其在抑制针对乳腺癌的免疫反应中的潜在作用。
