Dynamic changes in the T cell receptor repertoire during treatment with radiotherapy combined with an immune checkpoint inhibitor. Issue 11 (1st September 2021)

• Record Type: Journal Article
• Authors: Öjlert, Åsa Kristina; Nebdal, Daniel; Snapkov, Igor; Olsen, Vibeke; Kidman, Joel; Greiff, Victor; Chee, Jonathan; Helland, Åslaug
• Is Part Of: Molecular oncology. Volume 15:Issue 11(2021)
• Page Start: 2958
• Page End: 2968
• Publication Date: 2021-09-01
• Subjects: abscopal response -- immunotherapy -- non‐small cell lung cancer -- radiotherapy -- T cell receptor sequencing; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.13082
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : 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. Abstract : Radiotherapy and immunotherapy have been proposed to work synergistically in the treatment of cancer. We used T cell receptor (TCR) sequencing to monitor the immunological response to combined stereotactic radiotherapy and PD‐L1 blockade in patients with metastatic non‐small cell lung cancer. Specifically, we investigated possible mechanisms of action and the potential of the TCR repertoire as a dynamic biomarker.