Open AccessDynamic changes in the T cell receptor repertoire during treatment with radiotherapy combined with an immune checkpoint inhibitor
Author(s) -
Öjlert Åsa Kristina,
Nebdal Daniel,
Snapkov Igor,
Olsen Vibeke,
Kidman Joel,
Greiff Victor,
Chee Jonathan,
Helland Åslaug
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13082
Subject(s) - t cell receptor , immunotherapy , radiation therapy , repertoire , biology , immune system , immune checkpoint , lung cancer , cancer research , cancer immunotherapy , blockade , cancer , immunology , t cell , oncology , receptor , medicine , genetics , physics , acoustics
Previous studies have indicated a synergistic effect between radiotherapy and immunotherapy. A better understanding of how this combination affects the immune system can help to clarify its role in the treatment of metastatic cancer. We performed T cell receptor (TCR) sequencing on 46 sequentially collected samples from 15 patients with stage IV non‐small cell lung cancer, receiving stereotactic body radiotherapy combined with a programmed cell death ligand‐1 (PD‐L1) inhibitor. TCR repertoire diversity was assessed using Rényi diversity curves and the Shannon diversity index. TCR clones were tracked over time. We found decreasing or stable diversity in the best responders, and an increase in diversity at progression in patients with an initial response. Expansion of TCR clones was more often seen in responders. Several patients also developed new clones of high abundance. This seemed to be more related to radiotherapy than to immune checkpoint blockade. In summary, we observed similar dynamics in the TCR repertoire as have been described with immunotherapy alone. In addition, the occurrence of new unique clones of high abundance after radiotherapy may indicate that radiotherapy functions as a personalized cancer vaccine.