Abstract:Cancer immunotherapy is a major breakthrough in the history of tumor therapy in the last decade. Immune checkpoint inhibitors blocking CTLA-4/B7 or PD-1/PD-L1 pathways have greatly prolonged the survival of patients with different cancers. Long non-coding RNAs (lncRNAs) are abnormally expressed in tumors and play an important role in tumor immunotherapy through immune regulation and immunotherapy resistance. In this review, we summarized the mechanisms of lncRNAs in regulating gene expression and well-studied … Show more
“…LncRNAs are recently gaining more attention in cancer research due to their high versatility in regulating gene expression. Many studies have already shown the role of lncRNAs in cancer hallmarks, and over the past years, the literature on the relation between lncRNAs and tumor immune response has grown significantly [27][28][29][30][31].…”
Section: Lncrnas and Immune Response: The Pd-1/pd-l1 Pathwaymentioning
confidence: 99%
“…An integrative analysis of lncRNAs associated with tumor immune response including over 9000 samples across 32 cancer types was able to define a score (LIMER-lincRNA-based immune response) able to predict immune cell infiltration and prognosis [31]. In the same study, the authors described that lincRNA EPIC1 (epigenetically induced lincRNA-1) interacts with the histone methyltransferase EZH2, leading to the epigenetic silencing of several genes, including MHC-I genes, representing a possible mechanism of tumor immune evasion and, thus, resistance to immunotherapy.…”
Section: Lncrnas and Pd-1/pdl-1 Axis In Other Cancer Typesmentioning
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.
“…LncRNAs are recently gaining more attention in cancer research due to their high versatility in regulating gene expression. Many studies have already shown the role of lncRNAs in cancer hallmarks, and over the past years, the literature on the relation between lncRNAs and tumor immune response has grown significantly [27][28][29][30][31].…”
Section: Lncrnas and Immune Response: The Pd-1/pd-l1 Pathwaymentioning
confidence: 99%
“…An integrative analysis of lncRNAs associated with tumor immune response including over 9000 samples across 32 cancer types was able to define a score (LIMER-lincRNA-based immune response) able to predict immune cell infiltration and prognosis [31]. In the same study, the authors described that lincRNA EPIC1 (epigenetically induced lincRNA-1) interacts with the histone methyltransferase EZH2, leading to the epigenetic silencing of several genes, including MHC-I genes, representing a possible mechanism of tumor immune evasion and, thus, resistance to immunotherapy.…”
Section: Lncrnas and Pd-1/pdl-1 Axis In Other Cancer Typesmentioning
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.
“…Recent studies highlight the unique epigenetic landscape exhibited by exhausted T cells. − Long non-coding RNA (lncRNA) and microRNA (miRNA) have emerged as key players regulating various biological functions, including T-cell activation, development, and differentiation. − DNA methylation, a crucial epigenetic modification, is another essential regulatory factor significantly affecting gene expression in various cellular processes . The availability of comprehensive epigenetic data has opened new avenues for investigating TEX holistically.…”
Exhausted T cells are a key component of immune cells that play a crucial role in the immune response against cancer and influence the efficacy of immunotherapy. Accurate assessment and measurement of T-cell exhaustion (TEX) are critical for understanding the heterogeneity of TEX in the tumor microenvironment (TME) and tailoring individualized immunotherapeutic strategies. In this study, we introduced DeepEpiTEX, a novel computational framework based on deep neural networks, for inferring the developmental hierarchy and functional states of exhausted T cells in the TME from epigenetic profiles. DeepEpiTEX was trained using various modalities of epigenetic data, including DNA methylation data, microRNA expression data, and long noncoding RNA expression data from 30 bulk solid cancer types in the TCGA pan-cancer cohort, and identified five optimal TEX subsets with significant survival differences across the majority of cancer types. The performance of DeepEpiTEX was further evaluated and validated in external multi-center and multi-type cancer cohorts, consistently demonstrating its generalizability and applicability in different experimental settings. In addition, we discovered the potential relationship between TEX subsets identified by DeepEpiTEX and the response to immune checkpoint blockade therapy, indicating that individuals with immune-favorable TEX subsets may experience the greatest benefits. In conclusion, our study sheds light on the role of epigenetic regulation in TEX and provides a powerful and promising tool for categorizing TEX in different disease settings.
“…According to other studies, HOTAIR functions as a trans-acting lncRNA and is linked to stomach cancer. According to a publication, overexpression of HOTAIR may encourage the growth of cancer cells in tissues by causing metastasis to spread to additional sites and organs [ 25 ]. Fig.…”
Colorectal cancer (CRC) and gastric cancer (GC) are major contributors to cancer-related mortality worldwide. Despite advancements in understanding molecular mechanisms and improved drug treatments, the overall survival rate for patients remains unsatisfactory. Metastasis and drug resistance are major challenges contributing to the high mortality rate in both CRC and GC. Recent research has shed light on the role of long noncoding RNAs (lncRNAs) in the development and progression of these cancers. LncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions with microRNAs (miRNAs) and proteins. They can serve as miRNA precursors or pseudogenes, modulating gene expression at transcriptional and post-transcriptional levels. Additionally, circulating lncRNAs have emerged as non-invasive biomarkers for the diagnosis, prognosis, and prediction of drug therapy response in CRC and GC. This review explores the intricate relationship between lncRNAs and CRC/GC, encompassing their roles in cancer development, progression, and chemoresistance. Furthermore, it discusses the potential of lncRNAs as therapeutic targets in these malignancies. The interplay between lncRNAs, miRNAs, and tumor microenvironment is also highlighted, emphasizing their impact on the complexity of cancer biology. Understanding the regulatory landscape and molecular mechanisms governed by lncRNAs in CRC and GC is crucial for the development of effective diagnostic and prognostic biomarkers, as well as novel therapeutic strategies. This review provides a comprehensive overview of the current knowledge and paves the way for further exploration of lncRNAs as key players in the management of CRC and GC.
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