ArticleJournal for immunotherapy of cancer2020
Blood-based kinase activity profiling: a potential predictor of response to immune checkpoint inhibition in metastatic cancer.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Blood-based kinase activity profiling to predict response to immune checkpoint inhibitors in patients with advanced stage NSCLC: the prospective IOpener study.Journal for immunotherapy of cancer · 2026Article
- Kinase signaling in liver disease via clinical-trial-on-a-PamChip: A distinctive methodology for drug mechanisms and personalized medicine.The Journal of biological chemistry · 2026Article
- Peripheral blood biomarkers for predicting response to PD-1/PD-L1 inhibitors.Biomarker research · 2026Review
- The HCV-Dependent Inhibition of Nrf1/ARE-Mediated Gene Expression Favours Viral Morphogenesis.Viruses · 2025Article
- Predicting response to immunotherapy in lung cancer: an early HTA of predictive tests.International journal of technology assessment in health care · 2025Article
- Differential impact of hepatitis delta virus replication and expression of viral antigens on the cellular kinome profile.Cell communication and signaling : CCS · 2025Article
- FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases.Cellular and molecular life sciences : CMLS · 2024Article
- Antagonism of epidermal growth factor receptor signaling favors hepatitis E virus life cycle.Journal of virology · 2024Article
- The impact of HBx protein on mitochondrial dynamics and associated signaling pathways strongly depends on the hepatitis B virus genotype.Journal of virology · 2024Article
- Targeting glucosylceramide synthase induces antiproliferative and proapoptotic effects in osimertinib-resistant NSCLC cell models.Scientific reports · 2024Article
- TGF-β mRNA levels in circulating extracellular vesicles are associated with response to anti-PD1 treatment in metastatic melanoma.Frontiers in molecular biosciences · 2024Article
- Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas.Cancers · 2022Article
- Organ-Specific, Fibroblast-Derived Matrix as a Tool for Studying Breast Cancer Metastasis.Cancers · 2021Article
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Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany cancer patients do not obtain clinical benefit from immune checkpoint inhibition. Checkpoint blockade targets T cells, suggesting that tyrosine kinase activity profiling of baseline peripheral blood mononuclear cells may predict clinical outcome.
methodsHere a total of 160 patients with advanced melanoma or non-small-cell lung cancer (NSCLC), treated with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) or anti-programmed cell death 1 (anti-PD-1), were divided into five discovery and cross-validation cohorts. The kinase activity profile was generated by analyzing phosphorylation of peripheral blood mononuclear cell lysates in a microarray comprising of 144 peptides derived from sites that are substrates for protein tyrosine kinases. Binary grouping into patients with or without clinical benefit was based on Response Evaluation Criteria in Solid Tumors V.1.1. Predictive models were trained using partial least square discriminant analysis (PLS-DA), performance of the models was evaluated by estimating the correct classification rate (CCR) using cross-validation.
resultsThe kinase phosphorylation signatures segregated responders from non-responders by differences in canonical pathways governing T-cell migration, infiltration and co-stimulation. PLS-DA resulted in a CCR of 100% and 93% in the anti-CTLA-4 and anti-PD1 melanoma discovery cohorts, respectively. Cross-validation cohorts to estimate the accuracy of the predictive models showed CCRs of 83% for anti-CTLA-4 and 78% or 68% for anti-PD-1 in melanoma or NSCLC, respectively.
conclusionBlood-based kinase activity profiling for response prediction to immune checkpoint inhibitors in melanoma and NSCLC revealed increased kinase activity in pathways associated with T-cell function and led to a classification model with a highly accurate classification rate in cross-validation groups. The predictive value of kinase activity profiling is prospectively verified in an ongoing trial.
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