OA04.2. Single Cell Transcriptomic and T-Cell Receptor Diversity Analysis of Peripheral Blood Lymphocytes Comparing Proton Versus Photon-Based Chemoradiation in Esophageal Cancer

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ID: 326205
2026
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Ranked #432 of 453 articles by views in diseases of the esophagus : official journal of the international society for diseases of the esophagus

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Abstract
Abstract Topic Esophageal Cancer: Oncology/Radiation Therapy Background Radiation-induced lymphopenia (RIL) is a common toxicity during and after chemoradiation (CRT) but can be significantly mitigated with proton therapy (PT). The objective of this study is to determine if quantitative sparing of lymphocytes could also result in qualitative improvements in lymphocytes after CRT with PT compared to photons in esophageal cancer patients. Methods Patients were prospectively enrolled for longitudinal blood collection before, during and after radiation treatment. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-gradient centrifugation and cryopreserved. PT were delivered with passive scattering protons. Photons were delivered with intensity modulated radiation therapy (IMRT). For this analysis, 20 patients (10 patients in each group) were propensity-score matched according to planning treatment volume, baseline ALC, histology, age and body mass index. Up to 3-4 timepoints were analyzed per patient. PBMC lymphocytes were isolated using STEMCELL magnetic affinity assay, fixed, and single-cell RNA (scRNA) and single-cell T cell receptor (scTCR) libraries were generated using PARSE TCR Mega Kit. Downstream analyses of sequencing data were performed using RStudio Seurat. Results For scRNAseq, >1.1 million cells and for scTCRseq, >0.9 million cells were analyzed. Both scRNA and scTCRseq shared cell-barcodes which allowed for overlaying clonality to the transcriptome for each cell. TCR clonality analysis showed no significant differences between the PT and IMRT groups at baseline, mid or end of treatment time points (Figure 1). However, during follow up after CRT, IMRT was associated with a significant depletion of unique TCR clones, whereas no significant clonal depletion was observed in the PT group. Clonal depletion was more pronounced beyond 2 months after CRT compared to within the first 2 months following CRT. Transcriptomic and TCR clonality analyses revealed that IMRT (compared to PT) markedly depleted T-cell diversity and activated effector and naïve T cell populations, particularly in the post-CRT period. Conclusion In this propensity-matched cohort study, quantitative lymphocyte sparing by PT appears to also improve qualitative sparing of lymphocyte diversity, particularly in naïve T-lymphocytes. This study supports the view that PT may be the optimal radiation modality when combined with therapies that may rely on an intact immune system.
Reference Key
openalex_W7204004817 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors
Journal diseases of the esophagus : official journal of the international society for diseases of the esophagus
Year 2026
DOI
10.1093/dote/doag077.031
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