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乳腺癌细胞系、类器官和共培养物中免疫调节生物标志物的可变内在表达。

Variable Intrinsic Expression of Immunoregulatory Biomarkers in Breast Cancer Cell Lines, Mammospheres, and Co-Cultures.

机构信息

Research Unit, Dr. Balmis University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Pintor Baeza 12, 03010 Alicante, Spain.

Medical Oncology Department, Dr. Balmis University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Pintor Baeza 12, 03010 Alicante, Spain.

出版信息

Int J Mol Sci. 2023 Feb 24;24(5):4478. doi: 10.3390/ijms24054478.

Abstract

Advances in immunotherapy have increased interest in knowing the role of the immune system in breast cancer (BC) pathogenesis. Therefore, immune checkpoints (IC) and other pathways related to immune regulation, such as JAK2 and FoXO1, have emerged as potential targets for BC treatment. However, their intrinsic gene expression in vitro has not been extensively studied in this neoplasia. Thus, we evaluated the mRNA expression of tumor-cell-intrinsic (PD1), (PD-L1), (PD-L2), (B7-H3), , and in different BC cell lines, derived mammospheres, and co-cultures with peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction (qRT-PCR). Our results showed that intrinsic (PD-L1), and (PD-L2) were highly expressed in triple-negative cell lines, while was predominantly overexpressed in luminal cell lines. In contrast, and were under-expressed. Moreover, high levels of (PD1), (PD-L1), (PD-L2), and were found after mammosphere formation. Finally, the interaction between BC cell lines and peripheral blood mononuclear cells (PBMCs) stimulates the intrinsic expression of (PD1), (PD-L1), and (PD-L2). In conclusion, the intrinsic expression of immunoregulatory genes seems very dynamic, depending on BC phenotype, culture conditions, and tumor-immune cell interactions.

摘要

免疫疗法的进步增加了人们对免疫系统在乳腺癌(BC)发病机制中作用的兴趣。因此,免疫检查点(IC)和其他与免疫调节相关的途径,如 JAK2 和 FoXO1,已成为 BC 治疗的潜在靶点。然而,它们在这种肿瘤中的体外内在基因表达尚未得到广泛研究。因此,我们通过实时定量聚合酶链反应(qRT-PCR)评估了不同 BC 细胞系、衍生的类乳腺球体和与外周血单核细胞(PBMCs)共培养物中肿瘤细胞内在的(PD1)、(PD-L1)、(PD-L2)、(B7-H3)、、和 的 mRNA 表达。我们的结果表明,三阴性细胞系中内在的(PD-L1)和(PD-L2)高度表达,而 则主要在腔细胞系中过表达。相比之下,和则表达下调。此外,在类乳腺球体形成后发现 (PD1)、(PD-L1)、(PD-L2)和 水平升高。最后,BC 细胞系与外周血单核细胞(PBMCs)的相互作用刺激了内在的(PD1)、(PD-L1)和(PD-L2)表达。总之,免疫调节基因的内在表达似乎非常动态,取决于 BC 表型、培养条件和肿瘤免疫细胞相互作用。

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