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抗白细胞介素-8 单克隆抗体抑制乳腺癌肿瘤微环境中的自噬活性和癌症干细胞维持。

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

机构信息

Immunology and Allergy Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Faculty of Pharmacy, Department of Microbiology & Immunology, Pharos University in Alexandria, Alexandria, Egypt.

出版信息

Breast Dis. 2024;43(1):37-49. doi: 10.3233/BD-230052.

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.

摘要

背景

乳腺癌肿瘤微环境(TME)是免疫治疗的一个有前途的靶点。自噬和癌症干细胞(CSCs)的维持是肿瘤发生、肿瘤存活、侵袭和治疗耐药性所必需的过程。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、肿瘤生长增加、转移和预后不良有关。

目的

因此,我们旨在通过评估其对自噬活性和乳腺癌 CSC 维持的作用来研究针对 IL-8 的中和抗体的可能抗肿瘤作用。

方法

使用 IL-8 单克隆抗体补充来自 15 名接受乳房切除术的女性的肿瘤组织培养系统,使用免疫荧光技术评估 LC3B 作为自噬的特异性生物标志物的表达和 CD44、CD24 作为乳腺癌 CSCs 的细胞表面标志物。

结果

我们的结果表明,与正常乳腺组织相比,抗 IL-8 mAb 显著降低了培养的肿瘤组织中 LC3B 的水平。抗 IL-8 mAb 还显著降低了乳腺癌肿瘤或正常培养组织中 CD44 的表达。而在培养的乳腺癌组织中,它导致 CD24 表达的非显著降低,而在相应的正常组织中则导致其表达的显著降低。

结论

抗 IL-8 单克隆抗体通过靶向乳腺癌 TME 中的自噬和 CSCs 维持,表现出有希望的免疫治疗特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127c/10977415/ba67e22244a3/bd-43-bd230052-g001.jpg

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