P3.04-09 Analysis of Repertoire Features of T Cell Receptor in Treat-Naïve EGFR Wild-Type Lung Cancer Patients by High-Throughput Sequencing

Abstract

T cells can recognize peptides encoded by mutated genes. Assessment of the repertoire features of TCR is vital for us to deeper understand of immune behavior and immune response. However, detailed characterization of the peripheral blood T cell receptor (TCR) repertoire and its interaction with treat-naïve EGFR wild-type lung cancer patients have not been systemically studied. We used ultra-deep sequencing of rearranged genes in TCR β-chain (TCRβ) to profile the basic characteristics of T cells in peripheral blood samples of 27 treat-naïve EGFR wild-type lung cancer patients received chemotherapy as well as age- and gender-matched healthy donors without any history of cancer. Data showed that healthy donors had more TCR clonotypes and higher diversity while patients represented with restricted TCR repertoire. Interestingly, TCR repertoire was associated with TP53 mutation status, tumor volume, rapid progression and squamous cell carcinoma antigen (SCC) level in patients, but not with metastasis. Patients with TP53 mutation had fewer clonotypes (p=0.011), lower diversity (p=0.006) and higher clonality (p=0.054), while those with larger tumor volume and rapid progression following chemotherapy had fewer clonotypes (p=0.046 and p=0.011, respectively) in peripheral blood. peripheral blood TCR repertoire was not significant correlated with brain metastasis or bone metastasis. In addition, clonality was positive correlation with SCC Concentration (p=0.024,R=0.48,n=22). Our study promote a better knowledge about the T cells among treat-naïve EGFR wild-type lung cancer patients and provides new insight into the TCR repertoire associated with clinical presentation in lung cancer patients. And the TCR repertoire in peripheral blood samples before treatment may be used as a predictor of rapid progression in lung cancer patients treated with chemotherapy.