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01-12-2020 | NSCLC | Original Article

Dynamics of peripheral T cell clones during PD-1 blockade in non-small cell lung cancer

Authors: Fan Zhang, Hua Bai, Ranran Gao, Kailun Fei, Jianchun Duan, Zemin Zhang, Jie Wang, Xueda Hu

Published in: Cancer Immunology, Immunotherapy | Issue 12/2020

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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Title: Dynamics of peripheral T cell clones during PD-1 blockade in non-small cell lung cancer
Authors: Fan Zhang
Hua Bai
Ranran Gao
Kailun Fei
Jianchun Duan
Zemin Zhang
Jie Wang
Xueda Hu
Publication date: 01-12-2020
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Cancer Immunotherapy
Published in: Cancer Immunology, Immunotherapy / Issue 12/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02642-4

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