Immunomodulatory role for MicroRNAs: Regulation of PD-1/PD-L1 and CTLA-4 immune checkpoints expression
Najwa Skafi1, Mohammad Fayyad-Kazan1, Bassam Badran1
1Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon.
Abstract:
The development and progression of different pathologies including, cancer, are associated with suppressed immune responses. This restrained immune activity could be associated with the activation of different immune checkpoint pathways that mediate immunosuppressive functions. Therapeutic Protocols based on abolishing the activity of immune check points provided a promising potential for treating cancer. Among the distinct known immune checkpoints, PD-1/PD-L1 and CTLA-4, are the most studied and have been the focus for development of different blocking agents. Monoclonal antibodies that can block PD-1, PD-L1 or CTLA4 have been approved for treatment of different cancers. MicroRNAs (miRNAs), short non-coding regulatory RNA molecules, could repress mRNA expression at a post-transcriptional level. Many miRNAs have been reported to modulate the expression of CTLA-4 and PD-1/PD-L1, either directly or indirectly, in multiple pathological cases, mainly cancer. In this review, after a brief introduction about T cell activation and immune checkpoints, the miRNAs regulating the expression of CTLA-4 and PD-1/PD-L1 are discussed with highlights on their role in cancer. Many of these miRNAs could serve as novel treatments in different types of cancer as detailed throughout the review.
Insights
Immune checkpoints like PD-1/PD-L1 and CTLA-4 suppress anti-cancer immunity. MicroRNAs (miRNAs) regulate these checkpoints, offering potential new cancer treatments by modulating immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Cancer development is linked to suppressed immune responses, often mediated by immune checkpoint pathways.
- Immune checkpoints, particularly PD-1/PD-L1 and CTLA-4, are key targets for cancer immunotherapy.
- MicroRNAs (miRNAs) are regulatory RNA molecules influencing gene expression post-transcriptionally.
Purpose of the Study:
- To review the role of microRNAs in regulating immune checkpoints (CTLA-4 and PD-1/PD-L1).
- To highlight the significance of these miRNA-mediated regulations in various cancer types.
- To explore the potential of miRNAs as novel therapeutic agents in cancer treatment.
Main Methods:
- Literature review of studies on T cell activation, immune checkpoints, and microRNA regulation.
- Analysis of research detailing miRNA interactions with CTLA-4 and PD-1/PD-L1 pathways.
- Synthesis of findings on the impact of these interactions in cancer pathology.
Main Results:
- Numerous miRNAs directly or indirectly modulate the expression of CTLA-4 and PD-1/PD-L1.
- These miRNA regulations play a significant role in the immune microenvironment of various cancers.
- Specific miRNAs demonstrate potential for targeted cancer therapy.
Conclusions:
- MicroRNAs are critical regulators of key immune checkpoints (CTLA-4, PD-1/PD-L1) in cancer.
- Targeting these miRNAs presents a promising avenue for developing novel immunotherapies.
- Further research into miRNA-based cancer treatments is warranted.
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