GBP1 Facilitates Indoleamine 2,3-Dioxygenase Extracellular Secretion to Promote the Malignant Progression of Lung Cancer

Meng, Yinnan; Wang, Wei; Chen, Meng; Chen, Kuifei; Xia, Xinhang; Zhou, Suna; Yang, Haihua

doi:10.3389/fimmu.2020.622467

Cited by 15 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…GBP1and GBP2, as the most interferoninduced genes in the GTPase superfamily, participates in membrane, cytoskeleton and cell verification reactions. GBP1 facilitates extracellular secretion of IDO1 to inhibit the activity of T cells, and its expression level is related to the poor prognosis of NSCLC patients (62), while GBP2 promotes glioblastoma tumor growth and invasion in vivo and in vitro (63). Herein, immunogenetic characteristics such as TCR/BCR diversity, IMs, IPS, TIDE scores were utilized to quantify immunogenicity and response of ICIs for LUAD patients.…”

Section: Discussionmentioning

confidence: 99%

Cross-talk of pyroptosis and tumor immune landscape in lung adenocarcinoma

Wang¹,

Lin²,

Liu³

et al. 2021

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background: Pyroptosis has been reported to exhibit a crucial effect on tumorigenesis, development and immune regulation in cancers. However, the potential roles of pyroptosis in the tumor immune landscape remain elusive in lung adenocarcinoma (LUAD) patients. Methods: In this study, we curated 48 pyroptosis related genes (PRGs), used an unsupervised clustering method to determine pyroptosis patterns and comprehensively evaluated the pyroptosis patterns and tumor immune landscape of 500 LUAD patients. The Pyro score was developed using random survival forest algorithm, and multivariate Cox regression analysis was performed to evaluate the prognostic value of the Pyro score. Results: Based on the mRNA expression profiles of 48 PRGs, three pyroptosis patterns were identified with distinct prognosis, biological pathways and immune landscape. We characterized three pyroptosis patterns by differences in epithelial mesenchymal transition (EMT), extent of intratumor heterogeneity (ITH), overall cell proliferation, neoantigen load, T-cell receptor (TCR) diversity, expression of immunomodulatory genes, and patient prognosis. Meanwhile, the Pyro score was established and validated as an independent prognostic factor and immunotherapy predictor for LUAD. Patients with low Pyro score were characterized by prolonged survival time, enhanced immune infiltration. In response to anti-cancer drugs, patients with low Pyro score exhibited higher sensitivities of drugs which targeted oncogenic related pathways, such as DNA damage repair (DDR) and IGF-1R pathways, and especially increased response to anti-PD-1/L1 immunotherapy. Conclusions: This study revealed the cross-talk between pyroptosis and the tumor immune landscape in LUAD. The comprehensive evaluation of pyroptosis patterns in individual LUAD patients enhances our understanding of the tumor immune landscape and provides a new way toward personalized immunotherapeutic strategies for LUAD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Cross-talk of pyroptosis and tumor immune landscape in lung adenocarcinoma

Wang¹,

Lin²,

Liu³

et al. 2021

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…For instance, a previous study discovered that GBP1 could inhibit colorectal carcinoma progression [35]. On the contrary, in esophageal squamous cell carcinoma, lung cancer and prostate cancer, GBP1 could promote tumor development [36][37][38]. In addition, GBP1 overexpression is related to taxol resistance and has a critical role in the development of multidrug resistance [39].…”

Section: Discussionmentioning

confidence: 99%

Circ_0058608 contributes to the progression and taxol resistance of non-small cell lung cancer by sponging miR-1299 to upregulate GBP1

Xing

Wang²

2022

Anti-Cancer Drugs

View full text Add to dashboard Cite

Circular RNAs (circRNAs) act as key regulators in human cancers and chemoresistance. Here, we aimed to explore the role and mechanism of circ_0058608 in nonsmall cell lung cancer (NSCLC) and taxol resistance. The expression of circ_0058608, microRNA-1299 (miR-1299) and guanylate binding protein 1 (GBP1) mRNA was determined by quantitative real-time PCR. In-vitro and in-vivo assays were conducted using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), colony formation, transwell assays, flow cytometry and animal xenograft experiments. The interaction between miR-1299 and circ_0058608 or GBP1 was confirmed by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ_0058608 was overexpressed in NSCLC tissues/cells and taxol-resistant NSCLC tissues/ cells. Circ_0058608 knockdown inhibited NSCLC cell proliferation and metastasis and also suppressed tumor growth in vivo. Moreover, circ_0058608 knockdown increased taxol sensitivity by increasing taxol-induced apoptosis in taxol-resistant NSCLC cells. Moreover, circ_0058608 silencing enhanced taxol-induced tumor growth of NSCLC in vivo. MiR-1299 was a target of circ_0058608, and the effects of circ_0058608 knockdown on NSCLC cell progression and taxol resistance were reversed by miR-1299 inhibition. Additionally, miR-1299 could interact with GBP1, and miR-1299 suppressed NSCLC cell progression and taxol resistance by targeting GBP1. Furthermore, circ_0058608 could regulate GBP1 expression by sponging miR-1299. Circ_0058608 promoted the progression and taxol resistance of NSCLC by regulating the miR-1299/GBP1 axis.

show abstract

“…The interaction between GBP1 and IDO1 proteins additionally enhances the extracellular secretion of this enzyme. Meng et al demonstrated that inhibition of this interaction by stragaloside IV or astragaloside IV causes a decrease in the extracellular secretion of IDO1 and increases the antitumor effect of PD-1 inhibitors in lung cancer cells both in-vivo and in-vitro ( Table 1 ) [ 116 ].…”

Section: Modulation Of Kynurenine Pathway Activity In the Management Of Neoplastic Diseasesmentioning

confidence: 99%

“…In addition to direct inhibition of the enzyme, the authors outlined other targets that may be considered as potential therapeutic solutions for KP overactivation accompanying cancer progression. They include downregulation of IDO1, IDO2, TDO and KMO expression, upregulation of their proteasomal degradation rate, targeting upstream regulators of IDO1 expression and activation, such as JAK/STAT3 pathway and KIT tyrosine kinase or downstream effectors of the KP metabolites, such as general control nonderepressible-2 kinase and mammalian target of rapamycin kinase [ 40 , 103 , 115 , 116 , 123 , 126 , 127 , 128 , 144 ]. Furthermore, inhibition of extracellular IDO secretion or the direct targeting of particular KP metabolites using monoclonal antibodies as well as blocking the KP receptors such as AhR and G protein-coupled receptor 35, or TRP cellular transport mechanisms also should be taken into consideration for further therapeutic strategies [ 40 , 116 ].…”

Section: Summary and Future Directionsmentioning

confidence: 99%

“…They include downregulation of IDO1, IDO2, TDO and KMO expression, upregulation of their proteasomal degradation rate, targeting upstream regulators of IDO1 expression and activation, such as JAK/STAT3 pathway and KIT tyrosine kinase or downstream effectors of the KP metabolites, such as general control nonderepressible-2 kinase and mammalian target of rapamycin kinase [ 40 , 103 , 115 , 116 , 123 , 126 , 127 , 128 , 144 ]. Furthermore, inhibition of extracellular IDO secretion or the direct targeting of particular KP metabolites using monoclonal antibodies as well as blocking the KP receptors such as AhR and G protein-coupled receptor 35, or TRP cellular transport mechanisms also should be taken into consideration for further therapeutic strategies [ 40 , 116 ]. These mechanisms seem to be the most promising, because they may reduce the immunosuppressive tumor microenvironment conditions, regardless of the source and intensity of KYN synthesis.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

See 1 more Smart Citation

Kynurenines as a Novel Target for the Treatment of Malignancies

2021

View full text Add to dashboard Cite

Malignancies are unquestionably a significant public health problem. Their effective treatment is still a big challenge for modern medicine. Tumors have developed a wide range of mechanisms to evade an immune and therapeutic response. As a result, there is an unmet clinical need for research on solutions aimed at overcoming this problem. An accumulation of tryptophan metabolites belonging to the kynurenine pathway can enhance neoplastic progression because it causes the suppression of immune system response against cancer cells. They are also involved in the development of the mechanisms responsible for the resistance to antitumor therapy. Kynurenine belongs to the most potent immunosuppressive metabolites of this pathway and has a significant impact on the development of malignancies. This fact prompted researchers to assess whether targeting the enzymes responsible for its synthesis could be an effective therapeutic strategy for various cancers. To date, numerous studies, both preclinical and clinical, have been conducted on this topic, especially regarding the inhibition of indoleamine 2,3-dioxygenase activity and their results can be considered noteworthy. This review gathers and systematizes the knowledge about the role of the kynurenine pathway in neoplastic progression and the findings regarding the usefulness of modulating its activity in anticancer therapy.

show abstract

GBP1 Facilitates Indoleamine 2,3-Dioxygenase Extracellular Secretion to Promote the Malignant Progression of Lung Cancer

Cited by 15 publications

References 36 publications

Cross-talk of pyroptosis and tumor immune landscape in lung adenocarcinoma

Cross-talk of pyroptosis and tumor immune landscape in lung adenocarcinoma

Circ_0058608 contributes to the progression and taxol resistance of non-small cell lung cancer by sponging miR-1299 to upregulate GBP1

Kynurenines as a Novel Target for the Treatment of Malignancies

Contact Info

Product

Resources

About