Interferon α in cancer immunoediting: From elimination to escape

Vidal, Paolo S.

doi:10.1111/sji.12863

Cited by 40 publications

(23 citation statements)

References 90 publications

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“…And Nitric oxide has been found to be involved in immune response, in which its important synthase NOS2 could regulate macrophages, T cells, B cells, and myeloid derived suppressor cells. Interferon Alpha has been approving for the treatment of more than fourteen types of cancer, including hairy cell leukemia, melanoma, and renal cell carcinoma as an immune-based oncologic drug for years 60,61 . Collectively, these might help explain why patients in m 6 A high-risk group suffered from worse survival than those in m 6 A low-risk group on the molecular mechanism level.…”

Section: Discussionmentioning

confidence: 99%

Expression of N6-Methyladenosine (m6A) Regulators Correlates With Immune Microenvironment Infiltration and Predicts Prognosis in Diffuse Large Cell Lymphoma (DLBCL)

Xie

Hong

et al. 2021

Preprint

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Background: N6-methyladenosine (m6A) and immune microenvironment infiltration have been widely reported to play important roles in various cancers. However, in diffuse large cell lymphoma (DLBCL), the clinical significance of m6A regulators and their relationship with immune microenvironment infiltration have not been illuminated.Methods: The expression of m6A regulators in DLBCL was investigated using The Cancer Genome Atlas and Genotype-Tissue Expression databases. The capacity of m6A regulators in dividing molecular clusters of DLBCL was determined using Consensus Clustering algorithm and validated via principal component analysis. The clinical traits and prognosis difference in m6A-sorted clusters were revealed. The m6A prognostic signature was established and validated based on Gene Expression Omnibus dataset using univariate Cox and LASSO regression analysis. The immune cell infiltration and the expression of immune checkpoint genes in m6A low/high-risk DLBCL were studied. Gene set enrichment analysis (GSEA) was adopted to unveil the underlying molecular mechanism in m6A low/high-risk DLBCL.Results: Differentially expressed m6A regulators were able to molecularly discriminate DLBCL as two clusters based on consensus clustering and principal component analysis. A six m6A regulators-based risk prediction signature was established and validated as an independent predictor, which separated patients into m6A low- and high-risk groups. High-risk m6A indicates worse survival, for which the predictive AUC at 1-, 2-, and 5-year achieved 0.605, 0.640, and 0.652, respectively. Immune cell infiltration analysis revealed the B cells naïve and T cells gamma delta were the top increased and decreased immune cells in high-risk m6A patients. Up-regulated (PDCD1 and KIR3DL1) and down-regulated (TIGIT, DO1, and BTLA) immune checkpoint genes in high-risk m6A patients were identified. GSEA analysis unveiled high-risk m6A related to tumor proliferation associated process, while low-risk m6A related to defense response associated process. Conclusions: This study provided a comprehensive analysis for the clinical significance of m6A regulators and their association with immune microenvironment infiltration. An m6A regulators-based risk signature may be applied for the risk stratification of DLBCL patients, thus may facilitate the clinical management of DLBCL. Immune microenvironment was found to be closely related to m6A risk, which may be part of the mechanism of m6A regulators in DLBCL.

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Section: Discussionmentioning

confidence: 99%

Expression of N6-Methyladenosine (m6A) Regulators Correlates With Immune Microenvironment Infiltration and Predicts Prognosis in Diffuse Large Cell Lymphoma (DLBCL)

Xie

Hong

et al. 2021

Preprint

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“…Most likely, this is imputable to murine tumors having thrived in the NOD-SCID immuno-deficient context 21 . In passing, we note that interferon signaling is a prominent driver of cancer immuno-editing 22 , which raises the question whether immunotherapeutic approaches could be effective against FF+ iCCA.…”

Section: Both Imaging Methods Outlined the Cell Periphery (See Supplementioning

confidence: 99%

FGFR2 fusion protein-driven mouse models of intrahepatic cholangiocarcinoma unveil a necessary role for Erk signaling

Cristinziano

Porru

Lamberti

et al. 2020

Preprint

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All Authors, except M.J.B., have no personal, professional or financial conflicts to disclose. M.J.B. AbstractBackground and aims. About 15% of intrahepatic cholangiocarcinoma (iCCA) express fibroblast growth factor receptor 2 (FGFR2) fusion proteins (FFs), most often in concert with mutationally inactivated TP53, CDKN2A or BAP1. FFs span residues 1-768 of FGFR2 fused to sequences encoded by any of a long list (>60) of partner genes, a configuration sufficient to ignite oncogenic FF activation. In line, FGFR-specific tyrosine kinase inhibitors (F-TKI) were shown to provide clinical benefit in FF+ iCCA, although responses were partial and/or limited by resistance mechanisms, including the FF V565F gatekeeper mutation. Herein we present an FF-driven murine iCCA model and exploit its potential for pre-clinical studies on FF therapeutic targeting.Methods. Four iCCA FFs carrying different fusion sequences were expressed in Tp53 -/mouse liver organoids. Tumorigenic properties of genetically modified liver organoids were assessed by intrahepatic/subcutaneous transplantation in immuno-deficient mice. Cellular models derived from neoplastic lesions were exploited for pre-clinical studies. Results. Tumors diagnosed as CCA were obtained upon transplantation of FF-expressing liver organoids. The penetrance of this tumorigenic phenotype was influenced by FF identity. Tumor organoids and 2D cell lines derived from CCA lesions were addicted to FF signaling via Ras-Erk, regardless of FF identity or presence of V565F mutation. Double blockade of FF-Ras-Erk pathway by concomitant pharmacological inhibition of FFs and Mek1/2 provided greater therapeutic efficacy than single agent F-TKI in vitro and in vivo. Conclusions. FF-driven iCCA pathogenesis was successfully modelled in murine Tp53 -/background. This model revealed biological heterogeneity among structurally different FFs. Double blockade of FF-Erk signaling deserves consideration for improving precision-based approaches against human FF+ iCCA.

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“…When the virus infects target cells, RNA sensors induces IFN regulatory transcription factor translocation to the nucleus, which promotes type I IFN secretion. The secreted IFN interacts with IFN receptors on the cell membrane, which promotes phosphorylation of STAT1/2 transcriptional factors (127,128). The phosphorylated STAT1/2 localises to the nucleus, binds to IFN-stimulated response element responsible and activates IFN-stimulated genes, which then results in more production of type I IFN (129).…”

Section: Current Therapeutic Modalities For Covid-19mentioning

confidence: 99%

Approaches towards fighting the COVID‑19 pandemic (Review)

Tsai

Bau

et al. 2020

Int J Mol Med

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The coronavirus disease 2019 (cOVId-19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in recent years. Infection with COVID-19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID-19, SARS-CoV-2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID-19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID-19, characterizes the SARS-CoV-2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of anti-SARS-CoV-2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID-19 is discussed. It is expected that novel anti-viral agents, vaccines or an effective combination therapy for treatment/management of SARS-CoV-2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against cOVId-19. Contents 1. Introduction 2. Clinical characteristics of COVID-19 3. Structure, genome size and life cycle of SARS-CoV-2 4. Diagnostic methods for COVID-19 5. Methods to prevent cOVId-19 6. Current therapeutic modalities for COVID-19 7. Pharmacological agents targeting thrombosis 8. Neutralizing antibodies and vaccines against SARS-CoV-2 9. TcM and cOVId-19 10. conclusions

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Interferon α in cancer immunoediting: From elimination to escape

Cited by 40 publications

References 90 publications

Expression of N6-Methyladenosine (m6A) Regulators Correlates With Immune Microenvironment Infiltration and Predicts Prognosis in Diffuse Large Cell Lymphoma (DLBCL)

Expression of N6-Methyladenosine (m6A) Regulators Correlates With Immune Microenvironment Infiltration and Predicts Prognosis in Diffuse Large Cell Lymphoma (DLBCL)

FGFR2 fusion protein-driven mouse models of intrahepatic cholangiocarcinoma unveil a necessary role for Erk signaling

Approaches towards fighting the COVID‑19 pandemic (Review)

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