Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus

Mineo, Marco; Lyons, Shawn M.; Zdioruk, Mykola; Spreckelsen, Niklas von; Ferrer-Luna, Rubén; Ito, Hirotaka; Alayo, Quazim A.; Kharel, Prakash; Larsen, Alexandra Giantini; Fan, William Y.; Auduong, Sophia; Grauwet, Korneel; Passaro, Carmela; Khalsa, Jasneet Kaur; Shah, Khalid; Reardon, David A.; Ligon, Keith L.; Beroukhim, Rameen; Nakashima, Hiroshi; Ivanov, Pavel; Anderson, Paul J.; Lawler, Sean E.; Chiocca, E. Antonio

doi:10.1016/j.molcel.2020.05.015

Cited by 53 publications

(44 citation statements)

References 96 publications

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“…According to previous researches, lncRNAs were reported as crucial regulators in regulating cancer immunity [12]. A recent research from Mineo Marco et al reported that INCR1 knockdown can improve CAR T cell therapy via sensitizing tumor cells to cytotoxic T cell-mediated clearing [36]. Another research showed encouraging potentiality for new clinical management decisions on the basis of epigenetic regulation targeting LncMALAT1, which can coordinate with the immune system [37].…”

Section: Discussionmentioning

confidence: 99%

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

Xu¹,

Wang²,

Huang³

2020

Preprint

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Background: There have numerous evidences to support that long non-coding RNAs (lncRNAs) may be crucial parts in cancer immunity. We aimed to establish a novel and robust immune-associated lncRNAs signature to improve prognostic precision in patients with breast cancer(BRCA).Methods: BRCA cases were obtained from the The Cancer Genome Atlas (TCGA) database. Immune‐related lncRNAs presenting significant association with prognosis were screened through stepwise univariate Cox regression and LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, ROC analyses, and proportional hazards model further conducted. The prediction reliability was further estimated in the internal validation set and combination set. Gene set enrichment analysis (GSEA) was applied for functional annotation. The correlation between immune checkpoint inhibitors and this signature was employed. Results: 13 immune-related lncRNAs were systematically identified to establish immune-related lncRNAs predictive prognosis signature. The risk model we built showed significant correlation with BRCA patients’ prognosis. The value of ROC for this lncRNAs model was up to 0.821. This immune‐related lncRNAs signature can serve as an independent prognostic biomolecular factor. Our lncRNAs signature involved in chondrocyte development, endoderm development and so forth. This lncRNAs risk model was associated with tumor immune infiltration (i.e., B cells, Dendritic, Neutrophils, CD8 T cells and CD4 T cells, etc.,) and immune checkpoint blockade (ICB) therapy key molecules (i.e., PDCD1).Conclusion: The immune‐related lncRNA signature we established possesses latent prognostic value for patients with BRCA and may have the capability to predict the clinical outcome of ICB treatment, which could provide guidance for immunological decision in patients with BRCA.

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Section: Discussionmentioning

confidence: 99%

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

Xu¹,

Wang²,

Huang³

2020

Preprint

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“…According to previous researches, lncRNAs were reported as crucial regulators in regulating cancer immunity (13). A recent research from Mineo Marco et al reported that INCR1 knockdown can improve CAR T cell therapy via sensitizing tumor cells to cytotoxic T cell-mediated clearing (40). Another research showed encouraging potentiality for new clinical management decisions on the basis of epigenetic regulation targeting LncMALAT1, which can coordinate with the immune system (41).…”

Section: Discussionmentioning

confidence: 99%

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Pancreatic Ductal Adenocarcinoma

Xu¹,

Wang²,

Huang³

2020

Preprint

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Background: An increasing body of evidence has suggested that long non-coding RNAs (lncRNAs) can serve as essential regulators in cancer immunity. We aimed to establish a robust immune-associated lncRNA signature for pancreatic ductal adenocarcinoma (PDAC) outcome prediction to enhance prognostic accuracy.Methods: Pancreatic cancer samples were obtained from the The Cancer Genome Atlas (TCGA) project. Immune‐related lncRNAs displaying significant association with overall survival (OS) were screened through univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. The prediction reliability was further estimated in the internal validation set and combination set. Gene set enrichment analysis (GSEA) of the lncRNA model risk score was performed for functional annotation. The correlation between immune checkpoint inhibitors and this signature was examined. Results: 5 immune-related lncRNAs were confirmed to establish five‐immune-related lncRNAs prognostic signature. The constructed risk model showed significant correlation with PDAC OS. The area under the curve (AUC) for this lncRNA model was up to 0.747. This immune‐related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our signature mediated chondrocyte development, laminin binding and so forth. This risk score model was associated with immune cell infiltration (i.e., CD4 T cells, etc.,) and immune checkpoint blockade (ICB) immunotherapy‐related molecules (i.e., PDCD1 and CTLA4).Conclusion: The immune‐related lncRNA signature we established possesses latent prognostic value for patients with PDAC and may have the potential to measure the response to ICB immunotherapy, which could guide for immunological treatment in PDAC.

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“…LncRNA INCR1 binds hnRNPH1, preventing its negative effect on the expression of the neighboring genes PD-L1 and JAK2. This results in increased IFN-γ signaling and affects T cell-mediated clearance of tumor cells [ 197 ].…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

LncRNAs in the Type I Interferon Antiviral Response

Suarez

Prats-Mari

Unfried

et al. 2020

IJMS

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The proper functioning of the immune system requires a robust control over a delicate equilibrium between an ineffective response and immune overactivation. Poor responses to viral insults may lead to chronic or overwhelming infection, whereas unrestrained activation can cause autoimmune diseases and cancer. Control over the magnitude and duration of the antiviral immune response is exerted by a finely tuned positive or negative regulation at the DNA, RNA, and protein level of members of the type I interferon (IFN) signaling pathways and on the expression and activity of antiviral and proinflammatory factors. As summarized in this review, committed research during the last decade has shown that several of these processes are exquisitely regulated by long non-coding RNAs (lncRNAs), transcripts with poor coding capacity, but highly versatile functions. After infection, viruses, and the antiviral response they trigger, deregulate the expression of a subset of specific lncRNAs that function to promote or repress viral replication by inactivating or potentiating the antiviral response, respectively. These IFN-related lncRNAs are also highly tissue- and cell-type-specific, rendering them as promising biomarkers or therapeutic candidates to modulate specific stages of the antiviral immune response with fewer adverse effects.

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Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus

Abstract: Highlights d INCR1 is expressed from the PD-L1 locus in interferonstimulated tumor cells d INCR1 regulates tumor interferon signaling d Silencing INCR1 sensitizes tumor cells to T cell-mediated killing d INCR1 binds HNRNPH1 to promote PD-L1 and JAK2 expression

Cited by 53 publications

References 96 publications

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Pancreatic Ductal Adenocarcinoma

LncRNAs in the Type I Interferon Antiviral Response

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