Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC
Abstract Background Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomi...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-02-01
|
| Series: | Cancer Immunology, Immunotherapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s00262-024-03935-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract Background Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomic profiling of the systemic T cell response following SABR, with or without preceding immunotherapy/chemotherapy. Methods We conducted single-cell RNA and T cell receptor (TCR) sequencing of T cells from peripheral blood of seven patients with early-stage NSCLC taken pre- and post-SABR without or with prior immunotherapy and chemotherapy (icSABR). Other flow cytometry, single-cell RNA-seq data and bulk RNA-seq data were used to validate the results. Results We uncovered distinct T cell response patterns induced by these treatments: while terminal effector CD8+ T cells showed increased cytotoxic and inhibitory scores, and upregulated immune-activated pathways post-SABR, the reverse responses occurred post-icSABR. Furthermore, the proportion of large T cell clones increased and single clone decreased post-SABR, while the opposite was seen post-icSABR. Of note, both SABR and icSABR largely changed TCR clonotypes, which were mainly large clones post-SABR but single clone post-icSABR, and predominantly from terminal effector CD8+ T cells and T helper cells, respectively. Conclusions These findings reveal a complex interplay between SABR and immunotherapy, with potentially valuable implications for treatment strategies involving SABR and immunotherapy to induce systemic T cell responses for tumor eradication in patients with NSCLC. |
|---|---|
| ISSN: | 1432-0851 |