ArticleCancer management and research2020
A Novel Epitope Quality-Based Immune Escape Mechanism Reveals Patient's Suitability for Immune Checkpoint Inhibition.
Article in Cancer management and research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies.International journal of molecular sciences · 2023Article
- Proteasomal Processing Immune Escape Mechanisms in Platinum-Treated Advanced Bladder Cancer.Genes · 2022Article
- Digital gene expression analysis of NSCLC-patients reveals strong immune pressure, resulting in an immune escape under immunotherapy.BMC cancer · 2022Article
- Engineering neoantigen vaccines to improve cancer personalized immunotherapy.International journal of biological sciences · 2022Review
- Digital Gene Expression Analysis of Epithelioid and Sarcomatoid Mesothelioma Reveals Differences in Immunogenicity.Cancers · 2021Article
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15 authors.
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Abstract
backgroundImmune checkpoint inhibition, especially the blockade of PD-1 and PD-L1, has become one of the most thriving therapeutic approaches in modern oncology. Immune evasion caused by altered tumor epitope processing (so-called processing escapes) may be one way to explain immune checkpoint inhibition therapy failure. In the present study, we aim to demonstrate the effects of processing escapes on immunotherapy outcome in NSCLC patients. PATIENTS AND
methodsWhole exome sequencing data of 400 NSCLC patients (AdC and SCC) were extracted from the TCGA database. The ICB cohort was composed of primary tumor probes from 48 NSCLC patients treated with nivolumab. Mutations were identified by targeted amplicon-based sequencing including hotspots and whole exomes of 22 genes. The effect of mutations on proteasomal processing was evaluated by deep learning methods previously trained on 1260 known MHC-I ligands. Cox regression modelling was used to determine the influence on overall survival.
resultsIn the TCGA cohort, processing escapes were associated with decreased overall survival (p= 0.0140). In the ICB cohort, patients showing processing escapes in combination with high levels of PD-L1 (n=8/48) also showed significantly decreased overall survival, independently of mutational load or PD-L1 status.
conclusionThe concept of altered epitope processing may help to understand immunotherapy failure. Especially when combined with PD-L1 status, this method can be used as a biomarker to identify patients not suitable for immunotherapy.
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