原发性三阴性和雌激素受体阳性乳腺癌中 Siglec-7 和 Siglec-9 的表达及体外信号传导

IF 4.6 2区 医学 Q2 IMMUNOLOGY Clinical & Translational Immunology Pub Date : 2024-09-06 DOI:10.1002/cti2.1524
Eline JH van Houtum, Anne HC Valk, Daniel Granado, Jasper Lok, Lune van den Bogaard, Naomi Remkes, Jesper van Eck van der Sluijs, Paul N Span, Lenneke AM Cornelissen, Gosse J Adema
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引用次数: 0

摘要

目的 PD-1/PD-L1 免疫检查点阻断疗法是治疗晚期乳腺癌患者的有效方法。然而,雌激素受体阳性(ER+)肿瘤患者往往只有少量淋巴细胞浸润,而大部分三阴性(TN)乳腺肿瘤患者不会产生有效的免疫治疗反应。因此,必须开发新的治疗策略。在此,我们研究了 Siglec-7 和 Siglec-9,它们是新型的 ITIM 抑制性免疫检查点受体,类似于 PD-1,但在更广泛的免疫细胞上表达。 方法 我们评估了 Siglec-7 和 Siglec-9(配体)在 TN 和 ER+ 乳腺癌肿瘤中的表达及其乳腺癌细胞系诱导的信号传导。 结果 我们发现,Siglec-7 和 Siglec-9 在 TN 肿瘤中高表达,而在 ER+ 肿瘤中低表达。髓系细胞、T 细胞和 NK 细胞中均可观察到 Siglec-7 的表达,而髓系细胞中则优先观察到 Siglec-9。在TN和ER+乳腺癌组织切片中都观察到了包括Siglec-7和Siglec-9配体在内的硅聚糖的表达。体外培养的 TN 细胞系中 Siglec-7 和 Siglec-9 配体的表达水平高于 ER+ 细胞系。重要的是,通过应用嵌合 Siglec-7 报告细胞,我们发现多个 TN 细胞系诱导了 Siglec-7 信号,但只有一个 ER+ 细胞系诱导了 Siglec-7 信号。此外,Siglec-7 信号与乳腺癌细胞系的 Siglec-7 配体表达水平直接相关。 结论 这些数据表明,针对 Siglec 受体的免疫疗法对目前治疗策略无效且肿瘤显示高免疫细胞浸润的 TN 乳腺癌患者尤为有效。
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Siglec-7 and Siglec-9 expression in primary triple negative and oestrogen receptor positive breast cancer and in vitro signalling

Objectives

PD-1/PD-L1 immune checkpoint blockade can be an effective treatment for advanced breast cancer patients. However, patients with oestrogen receptor positive (ER+) tumors often display only low lymphocyte infiltration, while a large part of triple negative (TN) breast tumors does not generate an effective immunotherapy response. Therefore, new treatment strategies have to be developed. Here, we investigate Siglec-7 and Siglec-9 as novel ITIM-bearing inhibitory immune checkpoint receptors similar to PD-1, but expressed on a broader range of immune cells.

Methods

We assessed Siglec-7 and Siglec-9 (ligand) expression in TN and ER+ breast cancer tumors and their breast cancer cell line-induced signalling.

Results

We report that Siglec-7 and Siglec-9 are highly expressed in TN tumors, and to a low extent in ER+ tumors. Siglec-7 was observed on myeloid cells, T cells, and NK cells and Siglec-9 preferentially on myeloid cells. Expression of sialoglycans, including Siglec-7 and Siglec-9 ligands, was observed in both TN and ER+ breast cancer tissue sections. Expression levels of Siglec-7 and Siglec-9 ligands were higher on in vitro cultured TN cell lines than ER+ cell lines. Importantly, by applying chimeric Siglec-7 reporter cells, we showed the induction of Siglec-7 signalling by multiple TN cell lines, but only by one ER+ cell line. Moreover, Siglec-7 signalling is directly related to Siglec-7 ligand expression levels of breast cancer cell lines.

Conclusion

These data imply that immunotherapy targeting Siglec receptors may be particularly interesting for TN breast cancer patients not responding to current treatment strategies with tumors displaying high immune cell infiltration.

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来源期刊
Clinical & Translational Immunology
Clinical & Translational Immunology Medicine-Immunology and Allergy
CiteScore
12.00
自引率
1.70%
发文量
77
审稿时长
13 weeks
期刊介绍: Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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