Combined chemoradiotherapy and programmed cell death‐ligand 1 blockade leads to changes in the circulating T‐cell receptor repertoire of patients with non‐small‐cell lung cancer. Issue 12 (21st September 2022)

• Record Type: Journal Article
• Authors: Someya, Masanori; Tokita, Serina; Kanaseki, Takayuki; Kitagawa, Mio; Hasegawa, Tomokazu; Tsuchiya, Takaaki; Fukushima, Yuki; Gocho, Toshio; Kozuka, Yoh; Mafune, Shoh; Ikeuchi, Yutaro; Takahashi, Mamoru; Moniwa, Keigo; Matsuo, Kazuhiko; Hasegawa, Tadashi; Torigoe, Toshihiko; Sakata, Koh‐ichi
• Is Part Of: Cancer science. Volume 113:Issue 12(2022)
• Page Start: 4394
• Page End: 4400
• Publication Date: 2022-09-21
• Subjects: immune checkpoint blockade -- immune surveillance -- lung cancer -- radiotherapy -- T cell; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15566
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Combined chemoradiotherapy (CRT) and programmed cell death‐ligand 1 (PD‐L1) blockade is a new care standard for unresectable stage III non‐small‐cell lung cancer (NSCLC). Although this consolidation therapy has improved the overall survival of patients with NSCLC, the synergistic action mechanisms of CRT and immunotherapy on T cells remain unclear. In addition, there is a paucity of reliable biomarkers to predict clinical responses to therapy. In this study, we analyzed T‐cell receptor (TCR) sequences in the peripheral blood of five patients with NSCLC. T‐cell receptor analysis was undertaken before treatment, after CRT, and after PD‐L1 blockade. Notably, we observed the expansion and alteration of the dominant T‐cell clonotypes in all cases with a complete response. In contrast, neither expansion nor alteration of the TCR repertoire was observed in cases with progressive disease. T cell expansion was initiated after CRT and was further enhanced after PD‐L1 blockade. Our findings suggest the systemic effect of CRT on circulating T cells in addition to the curative effect on limited tumor sites. Dynamic changes in circulating T‐cell clonotypes could have a prognostic significance for combined CRT and PD‐L1 blockade. Abstract : This study analyzed TCR sequences in the peripheral blood of patients with NSCLC before and after combined chemoradiotherapy and PD‐L1 blockade. The analysis found the expansion of the dominant T‐cell clonotypes in the cases with a complete response. These findings suggest the systemic effect of CRT on circulating T cells, which may have a prognostic significance.