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PD-1/PD-L1 Inhibitors Response in Triple-Negative Breast Cancer: Can Long Noncoding RNAs Be Associated?
Carolina Mathias1, Vanessa Nascimento Kozak1, Jessica Maria Magno2
1Post-Graduation Program in Genetics, Department of Genetics, Federal University of Parana, Curitiba 81530-980, Brazil.
Abstract:
As immune checkpoint inhibitors (ICI) emerge as a paradigm-shifting treatment option for patients with advanced or metastatic cancer, there is a growing demand for biomarkers that can distinguish which patients are likely to benefit. In the case of triple-negative breast cancer (TNBC), characterized by a lack of therapeutic targets, pembrolizumab approval for high-risk early-stage disease occurred regardless of PD-L1 status, which keeps the condition in a biomarker limbus. In this review, we highlight the participation of long non-coding RNAs (lncRNAs) in the regulation of the PD-1/PD-L1 pathway, as well as in the definition of prognostic immune-related signatures in many types of tumors, aiming to shed light on molecules that deserve further investigation for a potential role as biomarkers. We also conducted a bioinformatic analysis to investigate lncRNAs already investigated in PD-1/PDL-1 pathways in other cancer types, considering the TNBC molecular context. In this sense, from the generated data, we evidence here two lncRNAs, UCA1 and HCP5, which have not yet been identified in the context of the tumoral immune response in breast cancer. These candidates can be further explored to verify their use as biomarkers for ICI response. In this article, we present an updated review regarding the use of lncRNA as biomarkers of response to ICI, highlighting the versatility of using these molecules.
Insights
Long non-coding RNAs (lncRNAs) show promise as biomarkers for predicting response to immune checkpoint inhibitors (ICI) in cancer. This review highlights UCA1 and HCP5 as potential biomarkers for triple-negative breast cancer (TNBC) immunotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment, but effective biomarkers are needed to predict patient response.
- Triple-negative breast cancer (TNBC) lacks specific therapeutic targets, and current biomarkers like PD-L1 status are insufficient for guiding ICI therapy.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer and immune regulation.
Purpose of the Study:
- To review the role of lncRNAs in regulating the PD-1/PD-L1 pathway and their potential as prognostic biomarkers.
- To identify novel lncRNA candidates for predicting ICI response in TNBC through bioinformatic analysis.
- To highlight the potential of lncRNAs as versatile biomarkers for immunotherapy.
Main Methods:
- Comprehensive literature review on lncRNAs, PD-1/PD-L1 pathway, and cancer biomarkers.
- Bioinformatic analysis of lncRNAs involved in PD-1/PD-L1 pathways in various cancer types.
- Focus on the molecular context of triple-negative breast cancer (TNBC).
Main Results:
- lncRNAs play a significant role in regulating the PD-1/PD-L1 immune checkpoint pathway.
- Bioinformatic analysis identified UCA1 and HCP5 as potential lncRNA biomarkers for ICI response in TNBC.
- These lncRNAs have not been previously associated with the tumoral immune response in breast cancer.
Conclusions:
- lncRNAs represent a promising class of molecules for developing novel biomarkers to guide ICI therapy.
- UCA1 and HCP5 warrant further investigation as potential predictive biomarkers for TNBC patients undergoing immunotherapy.
- The study underscores the versatility of lncRNAs in cancer immunotherapy and biomarker discovery.
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