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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Sequencing raw data is available at GSA (Genome Sequence Archive in BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences). The accession number is HRA000104. Gene expression profiling of individual T cell clones at different time points can be explored on https://188.8.131.52:3838/lcpd.
Differentially expressed gene
Immune checkpoint blockade
Non-small cell lung cancer
Programmed cell death protein 1
Programmed death-ligand 1
Single-cell RNA sequencing
T cell receptor
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We thank Xuefang Zhang and Fei Wang for assistance with flow cytometry. We thank the Computing Platform of the CLS (Peking University).
This project was supported by Beijing Advanced Innovation Center for Genomics at Peking University, National Natural Science Foundation of China (31530036, 91742203, 91942307, 81988101, 81630071), National Key Research and Development Project (2019YFC1315700) and CAMS Innovation Fund for Medical Sciences (CIFMS 2016-I2M-3-008).
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The authors report no financial interests or potential conflicts of interests.
This study was approved by the Research and Ethical Committee of Cancer Hospital, Chinese Academy of Medical Sciences, China and complied with relevant ethical regulations.
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Zhang, F., Bai, H., Gao, R. et al. Dynamics of peripheral T cell clones during PD-1 blockade in non-small cell lung cancer. Cancer Immunol Immunother (2020). https://doi.org/10.1007/s00262-020-02642-4
- Cancer immunotherapy
- Single cell sequencing
- Non-small cell lung cancer