Immunotherapy for non-small cell lung cancer (NSCLC), as a stand-alone and in combination therapy

Kaur, Jasmine; Elms, Jackson; Munn, Alan Leslie; Good, David A.; Wei, Ming Q.

doi:10.1016/j.critrevonc.2021.103417

Cited by 28 publications

(14 citation statements)

References 128 publications

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“…Immunotherapy that emerged recently has achieved promising results in the treatment of LUAD ( 45 ). In our work, a comprehensive analysis of tumor-infiltrating immune cells was further conducted to help to clarify the immune infiltration status between the two different risk groups.…”

Section: Discussionmentioning

confidence: 99%

Integrated single-cell and transcriptome sequencing analyses determines a chromatin regulator-based signature for evaluating prognosis in lung adenocarcinoma

et al. 2022

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BackgroundAccumulating evidence has highlighted the significance of chromatin regulator (CR) in pathogenesis and progression of cancer. However, the prognostic role of CRs in LUAD remains obscure. We aim to detect the prognostic value of CRs in LUAD and create favorable signature for assessing prognosis and clinical value of LUAD patients.MethodsThe mRNA sequencing data and clinical information were obtained from TCGA and GEO databases. Gene consensus clustering analysis was utilized to determine the molecular subtype of LUAD. Cox regression methods were employed to set up the CRs-based signature (CRBS) for evaluating survival rate in LUAD. Biological function and signaling pathways were identified by KEGG and GSEA analyses. In addition, we calculated the infiltration level of immunocyte by CIBERSORT algorithm. The expressions of model hub genes were detected in LUAD cell lines by real-time polymerase chain reaction (PCR).ResultsKEGG analysis suggested the CRs were mainly involved in histone modification, nuclear division and DNA modification. Consensus clustering analysis identified a novel CRs-associated subtype which divided the combined LUAD cohort into two clusters (C1 = 217 and C2 = 296). We noticed that a remarkable discrepancy in survival rate among two clusters. Then, a total of 120 differentially expressed CRs were enrolled into stepwise Cox analyses. Four hub CRs (CBX7, HMGA2, NPAS2 and PRC1) were selected to create a risk signature which could accurately forecast patient outcomes and differentiate patient risk. GSEA unearthed that mTORC1 pathway, PI3K/Akt/mTOR and p53 pathway were greatly enriched in CRBS-high cohort. Moreover, the infiltration percentages of macrophage M0, macrophage M2, resting NK cells, memory B cells, dendritic cells and mast cells were statistically significantly different in the two groups. PCR assay confirmed the differential expression of four model biomarkers.ConclusionsAltogether, our project developed a robust risk signature based on CRs and offered novel insights into individualized treatment for LUAD cases.

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Section: Discussionmentioning

confidence: 99%

Integrated single-cell and transcriptome sequencing analyses determines a chromatin regulator-based signature for evaluating prognosis in lung adenocarcinoma

et al. 2022

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“…Exploratory biomarker analyses demonstrated that a high score on a four-gene inflammatory signature (CD8A, STAT1, LAG3, and CD274) is correlated with better survival in the experimental arm than in the standard one [32] . The CheckMate 743 results led to the Food and Drug Administration (FDA) approval of nivolumab and ipilimumab combination in MPM patients in October 2020, followed by the European Medicines Agency (EMA) approval in June 2021 [33] .…”

Section: Co-targeting Of Ctla-4 and Pd1/pdl1 Axismentioning

confidence: 99%

Immunotherapy in malignant pleural mesothelioma: a long story ended in success

Bongiovanni¹,

Frassoldati²,

Calabrò³

2022

J Cancer Metastasis Treat

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Malignant pleural mesothelioma (MPM) is an aggressive and rare disease, mainly due to asbestos exposure, characterized by a poor prognosis. For almost two decades, platinum-based chemotherapy has been the only approved therapeutic regimen for first-line MPM, with an overall survival of 12 months. In the last years, the therapeutic scenario of different tumor types, including MPM, has dramatically changed due to immune checkpoint inhibition. The promising results of this approach have promoted new efforts into clinical research, and many trials investigating novel therapeutic combinations are currently ongoing. The aim of the present review is to provide a comprehensive overview of the most promising immunotherapeutic-based strategies currently under investigation for advanced MPM.

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“…While it affects the quality of patients' life, it also increases the global economic burden. Due to a large number of mutations and general heterogeneity in this type of cancer, the use of traditional therapies has been challenging [ 2 ]. Small molecule tyrosine kinase inhibitors and immunotherapy have brought unprecedented survival benefits to selected patients.…”

Section: Introductionmentioning

confidence: 99%

METTL14 Regulates PLAGL2/β-Catenin Signaling Axis to Promote the Development of Nonsmall Cell Lung Cancer

Zhou

Lai

Gao

et al. 2023

Journal of Oncology

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N6-methyladenosine (m6A) is an abundant eukaryotic mRNA modification involved in regulating the formation and metastasis of nonsmall cell lung cancer (NSCLC). We collected clinical NSCLC tissue and paracarcinoma tissue. Then methyltransferase-like 14 (METTL14), pleomorphic adenoma gene like-2 (PLAGL2), and β-catenin expressions were assessed using quantitative real-time PCR and western blot. PLAGL2, and β-catenin (nuclear) expressions were increased in NSCLC tissues. Cell proliferation, migration, invasion, and death were examined. PLAGL2 could activate β-catenin signaling to affect cell proliferation and migration abilities. RNA immunoprecipitation assay was operated to identify m6A modification levels of PLAGL2 after knockdown and overexpression of METTL14. PLAGL2 was regulated by METTL14-mediated m6A modification. Knockdown of METTL14 repressed cell proliferation, migration, and invasion, and promoted cell death. Interestingly, these effects were reversed when PLAGL2 was overexpressed. Finally, tumor formation in nude mice was performed to verify the role of the METTL14/PLAGL2/β-catenin signaling axis. Tumor formation in nude mice demonstrated METTL14/PLAGL2/β-catenin axis promoted NSCLC development in vivo. In brief, METTL14 promoted NSCLC development by increasing m6A methylation of PLAGL2 to activate β-catenin signaling. Our research provided essential clues for in-depth comprehension of the mechanism of NSCLC occurrence and development and also provided the basis for NSCLC treatment.

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Immunotherapy for non-small cell lung cancer (NSCLC), as a stand-alone and in combination therapy

Cited by 28 publications

References 128 publications

Integrated single-cell and transcriptome sequencing analyses determines a chromatin regulator-based signature for evaluating prognosis in lung adenocarcinoma

Integrated single-cell and transcriptome sequencing analyses determines a chromatin regulator-based signature for evaluating prognosis in lung adenocarcinoma

Immunotherapy in malignant pleural mesothelioma: a long story ended in success

METTL14 Regulates PLAGL2/β-Catenin Signaling Axis to Promote the Development of Nonsmall Cell Lung Cancer

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