Immunology and Allergy Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Faculty of Pharmacy, Department of Microbiology & Immunology, Pharos University in Alexandria, Alexandria, Egypt.
Breast Dis. 2024;43(1):37-49. doi: 10.3233/BD-230052.
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.
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.
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.
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.
Anti-IL-8 monoclonal antibody exhibits promising immunotherapeutic properties through targeting both autophagy and CSCs maintenance within breast cancer TME.
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。
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。
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。
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。
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。