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  • Title: Dynamics of peripheral T cell clones during PD-1 blockade in non-small cell lung cancer.
    Author: Zhang F, Bai H, Gao R, Fei K, Duan J, Zhang Z, Wang J, Hu X.
    Journal: Cancer Immunol Immunother; 2020 Dec; 69(12):2599-2611. PubMed ID: 32591861.
    Abstract:
    Understanding of the functional states and clonal dynamics of T cells after immune checkpoint blockade (ICB) is valuable for improving these therapeutic strategies. Here we performed Smart-seq2 single-cell RNA sequencing (scRNA-seq) analysis on 3,110 peripheral T cells of non-small cell lung cancer (NSCLC) patients before and after the initiation of programmed cell death protein 1 (PD-1) blockade. We identified individual peripheral T cell clones based on the full-length T cell receptor (TCR) sequences and monitored their dynamics during immunotherapy. We found a higher cytotoxic activity in the tumor-related CD4+ T cell clones than in the CD8+ T cell clones. Based on a large tumor-related CD4+ T cell clone, we observed a dramatically decreased abundance after progression, as well as a reduction in the percentage of PD-1+ T cells. We also detected 25 genes, such as CXCR4, DUSP2 and ZFP36, that were noticeably upregulated or downregulated following progression. In addition, the pseudotime trajectory of CD8+ T cell clones corresponded to the treatment time points, showing a decreased activity in the "cytokine and cytokine receptor interaction" pathway. These analyses provided an insight into the dynamics of peripheral T cell clones during PD-1 blockade in NSCLC.
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