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Natural Blockers of PD-1/PD-L1 Interaction for the Immunotherapy of Triple-Negative Breast Cancer-Brain Metastasis.

ABSTRACT: The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood-brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain. For a drug to traverse the BBB via passive diffusion, various physicochemical properties should be considered. Since natural medicine has been a key inspiration for the development of the majority of current medicines, in this paper, we review several naturally-derived molecules which have the potential for immunotherapy via blocking the interaction of programmed cell death protein-1 (PD-1) and its ligand, PD-L1. The mechanism of action, physicochemical properties and pharmacokinetics of these molecules and their theoretical potential to be used for the treatment of TNBC-BM are discussed.

SUBMITTER: Nakhjavani M

PROVIDER: S-EPMC9777321 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Natural Blockers of PD-1/PD-L1 Interaction for the Immunotherapy of Triple-Negative Breast Cancer-Brain Metastasis.

Nakhjavani Maryam M Shigdar Sarah S

Cancers 20221219 24

The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood-brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones ...[more]

PMID: 36551742

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Project description:Breast cancer metastasis to the brain, occurring in about 15-25% of cases, represents a major obstacle in the treatment of triple-negative breast cancer (TNBC). The molecular mechanisms driving this form of metastasis are still largely unknown. PD-L1, an immune checkpoint protein, is central to tumor immune evasion and has become a focus for immunotherapy development. While PD-L1 inhibitors have shown success in various cancer types, their effectiveness in TNBC brain metastases remains to be fully investigated. This highlights the urgent need to understand the complex interactions between metastatic brain tumors and the tumor microenvironment in TNBC patients. Gaining insights into these dynamics is crucial for developing new targeted therapies, including those that modulate the PD-L1 pathway, to better manage and treat TNBC brain metastases. We explore the impact of Capsanthin on the tumor microenvironment of brain metastases in triple-negative breast cancer (TNBC). Our results reveal that Capsanthin effectively inhibits the migration of brain metastasis TNBC cells. Furthermore, Capsanthin significantly reduces the expression of EZH2 and N-linked glycosylated PD-L1 proteins and mRNA in TNBC cells, encompassing both primary and metastatic sites, as well as in mesenchymal stem cells (3A6). Data from The Cancer Genome Atlas (TCGA) indicate that elevated expression levels of EZH2 correlate with poorer patient prognosis. Immunoprecipitation assays demonstrate a direct interaction between EZH2 and PD-L1 in brain metastases of TNBC, underscoring the pivotal role of the EZH2-PD-L1 axis. Additionally, Capsanthin was found to suppress the expression of epithelial-mesenchymal transition (EMT) markers in metastatic brain TNBC cells and mesenchymal stem cells. Our results suggest that Capsanthin can modulate the tumor microenvironment and inhibit key pathways involved in cancer progression, offering potential therapeutic benefits for patients with TNBC brain metastases.

Dataset Information

Natural Blockers of PD-1/PD-L1 Interaction for the Immunotherapy of Triple-Negative Breast Cancer-Brain Metastasis.

Publications

Natural Blockers of PD-1/PD-L1 Interaction for the Immunotherapy of Triple-Negative Breast Cancer-Brain Metastasis.

Similar Datasets

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