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2022 World Conference on Lung Cancer (ePosters)
EP16.01-030. Peripheral T-Cell Receptor Repertoire ...
EP16.01-030. Peripheral T-Cell Receptor Repertoire Profiling in Non-small Cell Lung Cancer Using an Amplicon-Based Sequencing Assay
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Researchers have developed an amplicon-based next-generation sequencing assay to characterize the peripheral T-cell receptor (TCR) repertoire in non-small cell lung cancer (NSCLC) patients. The assay uses a molecular-barcoded primer panel to detect TCR-beta CDR3 rearrangements in T-cell populations. The assay's analytical sensitivity is determined to be 1 genome equivalent copy in a background of 10,000 genome equivalent copies of DNA. The study analyzed the peripheral TCR repertoire of 92 metastatic NSCLC patients using genomic DNA extracted from peripheral blood. <br /><br />The researchers calculated the productive d50 index, which measures the diversity of T-cell clones, and found that it decreased with increasing number of somatic mutations detected through liquid biopsy. They also observed that patients positive for TP53 mutations in circulating tumor DNA had a higher productive d50 index compared to those negative for TP53 mutations. Among EGFR-positive patients treated with first-line tyrosine kinase inhibitor, non-responders had higher productive clonality compared to responders.<br /><br />The researchers highlight the ability of their assay to determine peripheral TCR repertoires non-invasively and monitor them over time. They suggest that this amplicon-based TCR sequencing method can complement plasma-based ctDNA testing to assess immunological status and potentially monitor treatment response in NSCLC patients.<br /><br />In conclusion, the study demonstrates differences in peripheral TCR repertoires based on molecular subtypes of NSCLC and treatment status. The researchers emphasize the potential of their assay for non-invasive monitoring of TCR repertoires in NSCLC patients. The work was supported by Lucence Diagnostics Pte Ltd, and the authors are employees of Lucence Health Inc or Lucence Diagnostics Pte Ltd.
Asset Subtitle
Zi Yi Wan
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Speaker
Zi Yi Wan
Topic
Tumour Biology and Biomarkers - Immune Biology & Immunotherapy
Keywords
amplicon-based next-generation sequencing
TCR repertoire
non-small cell lung cancer
molecular-barcoded primer panel
analytical sensitivity
liquid biopsy
TP53 mutations
productive d50 index
tyrosine kinase inhibitor
non-invasive monitoring
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