Anti-IL-8 monoclonal antibodies inhibits the autophagic activity and cancer stem cells maintenance within breast cancer tumor microenvironment.

Breast disease Pub Date : 2024-01-01 DOI:10.3233/BD-230052

Seham Abou Shousha, Eman M Osman, Suzan Baheeg, Yasmine Shahine

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引用次数: 0

Abstract

Background: Breast cancer tumor microenvironment (TME) is a promising target for immunotherapy. Autophagy, and cancer stem cells (CSCs) maintenance are essential processes involved in tumorigenesis, tumor survival, invasion, and treatment resistance. Overexpression of angiogenic chemokine interleukin-8 (IL-8) in breast cancer TME is associated with oncogenic signaling pathways, increased tumor growth, metastasis, and poor prognosis.

Objective: Thus, we aimed to investigate the possible anti-tumor effect of neutralizing antibodies against IL-8 by evaluating its efficacy on autophagic activity and breast CSC maintenance.

Methods: IL-8 monoclonal antibody supplemented tumor tissue culture systems from 15 females undergoing mastectomy were used to evaluate the expression of LC3B as a specific biomarker of autophagy and CD44, CD24 as cell surface markers of breast CSCs using immunofluorescence technique.

Results: Our results revealed that anti-IL-8 mAb significantly decreased the level of LC3B in the cultured tumor tissues compared to its non-significant decrease in the normal breast tissues.Anti-IL-8 mAb also significantly decreased the CD44 expression in either breast tumors or normal cultured tissues. While it caused a non-significant decrease in CD24 expression in cultured breast tumor tissue and a significant decrease in its expression in the corresponding normal ones.

Conclusions: Anti-IL-8 monoclonal antibody exhibits promising immunotherapeutic properties through targeting both autophagy and CSCs maintenance within breast cancer TME.

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抗IL-8单克隆抗体可抑制乳腺癌肿瘤微环境中的自噬活性和癌症干细胞的维持。

背景：乳腺癌肿瘤微环境（TME）是一个很有前景的免疫治疗靶点。自噬和癌症干细胞（CSCs）的维持是肿瘤发生、肿瘤存活、侵袭和耐药性的重要过程。乳腺癌TME中血管生成趋化因子白细胞介素-8（IL-8）的过表达与致癌信号通路、肿瘤生长、转移和预后不良有关：因此，我们旨在通过评估中和IL-8的抗体对自噬活性和乳腺癌CSC维持的作用，研究其可能的抗肿瘤效果：采用免疫荧光技术评估作为自噬特异性生物标志物的 LC3B 和作为乳腺 CSCs 细胞表面标志物的 CD44、CD24 的表达：结果：我们的研究结果显示，抗IL-8 mAb可显著降低培养肿瘤组织中LC3B的水平，而在正常乳腺组织中则无明显降低。抗IL-8 mAb还能明显降低CD44在乳腺肿瘤或正常培养组织中的表达，而在培养的乳腺肿瘤组织中，CD24的表达下降不明显，而在相应的正常组织中，CD24的表达则明显下降：结论：抗IL-8单克隆抗体通过靶向自噬和乳腺癌TME中CSCs的维持，表现出良好的免疫治疗特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Breast disease Medicine-Oncology

CiteScore

1.80

自引率

0.00%

发文量

期刊介绍： The recent expansion of work in the field of breast cancer inevitably will hasten discoveries that will have impact on patient outcome. The breadth of this research that spans basic science, clinical medicine, epidemiology, and public policy poses difficulties for investigators. Not only is it necessary to be facile in comprehending ideas from many disciplines, but also important to understand the public implications of these discoveries. Breast Disease publishes review issues devoted to an in-depth analysis of the scientific and public implications of recent research on a specific problem in breast cancer. Thus, the reviews will not only discuss recent discoveries but will also reflect on their impact in breast cancer research or clinical management.