In recent years, the C–C chemokine ligand 5/C–C chemokine receptor 5 (CCL5/CCR5) axis has emerged as an appealing therapeutic target in various malignant diseases, including solid tumors, hematological cancers, and even coronavirus disease 2019 (COVID-19) [[3], [4], [5], [6], [7], [8], [9], [10], [11]]. This axis plays a critical role in cancer progression by influencing tumor growth, extracellular matrix remodeling, cancer stem cell expansion, and drug resistance [8]. Additionally, the CCL5/CCR5 axis is implicated in diseases beyond cancer, such as diabetes and Alzheimer's disease [12,13]. The CCL5/CCR5 axis does not only have an impact on tumor cells, but also modulates immune cells within the tumor microenvironment [14,15]. However, the available tools for studying the function and mechanisms of the CCL5/CCR5 axis are limited, the current main approaches were relying on CCL5-targeted small interfering RNA (siRNA) or anti-CCL5 antibodies, in combination with or without the only FDA-approved CCR5 antagonist, maraviroc [6,16]. The absence of specific antagonists for the CCL5/CCR5 axis significantly hinders our understanding of its pathological activities and mechanisms across various diseases
To date, only a few pathways, like the phosphatidylinositol 3-kinase/protein kinase B (PI3K/PKB) pathway, have been reported to be regulated by the CCL5/CCR5 axis in cancers [5,17]. However, the precise molecular mechanisms and specific antagonists targeting this axis in TNBC tumor growth and metastasis remain poorly understood.
In this study, we have developed a cell-based high-throughput screening (HTS) assay to identify the antagonists of the CCL5/CCR5 axis for TNBC immunotherapy. By employing a drug repositioning approach, HTS, and multiple preclinical mouse models, we have identified verteporfin as not only a molecular probe for the CCL5/CCR5 axis, but also an immunotherapeutic agent for TNBC and other malignant cancers, including colon adenocarcinoma, pancreatic adenocarcinoma, low-grade glioma, and thymoma. Furthermore, we have unraveled the crucial role of CCR5 in regulating YAP1 oncogene, and elucidated the immune-dependent and cell-intrinsic mechanisms underlying the impact of the CCL5/CCR5 axis on TNBC tumor growth and metastasis.
Chinese scientists on CCR5/TNBC no mention of LL. How is that possible?
https://www.sciencedirect.com/science/article...3524000296
Credit Bluemoon on IVillage
To date, only a few pathways, like the phosphatidylinositol 3-kinase/protein kinase B (PI3K/PKB) pathway, have been reported to be regulated by the CCL5/CCR5 axis in cancers [5,17]. However, the precise molecular mechanisms and specific antagonists targeting this axis in TNBC tumor growth and metastasis remain poorly understood.
In this study, we have developed a cell-based high-throughput screening (HTS) assay to identify the antagonists of the CCL5/CCR5 axis for TNBC immunotherapy. By employing a drug repositioning approach, HTS, and multiple preclinical mouse models, we have identified verteporfin as not only a molecular probe for the CCL5/CCR5 axis, but also an immunotherapeutic agent for TNBC and other malignant cancers, including colon adenocarcinoma, pancreatic adenocarcinoma, low-grade glioma, and thymoma. Furthermore, we have unraveled the crucial role of CCR5 in regulating YAP1 oncogene, and elucidated the immune-dependent and cell-intrinsic mechanisms underlying the impact of the CCL5/CCR5 axis on TNBC tumor growth and metastasis.
Chinese scientists on CCR5/TNBC no mention of LL. How is that possible?
https://www.sciencedirect.com/science/article...3524000296
Credit Bluemoon on IVillage
3
