Dynamic immune profiling predicts response to radiation plus anti-PD-1 therapy in oligometastatic renal cell carcinoma
- Author(s)
- To, V; Thio, N; Castle, R; Macdonald, S; Molden-Hauer, T; Wells, J; McMahon, R; Bressel, M; Tran, B; Azad, AA; Moon, D; Appu, S; Wong, LM; Murphy, DG; Cuff, K; Pryor, D; Spain, L; Au, L; D'Souza, C; Neeson, PJ; Siva, S;
- Journal Title
- Nature Communications
- Publication Type
- Online publication before print
- Abstract
- Biomarkers that predict response to combined radiation and anti-PD-1 therapy in clear cell renal cell carcinoma (ccRCC) are poorly defined. RAPPORT trial (NCT02855203) is a prospective phase I/II study of stereotactic ablative body radiotherapy (SABR) and pembrolizumab in 30 patients with oligometastatic ccRCC. The primary endpoint was safety; secondary endpoints included overall survival, time to local progression, distant progression-free survival, objective and disease control rates, duration of response and patient-reported pain. Here, we report the pre-specified exploratory translational analyses. In pre-treatment tumours, responders had greater intra-tumoural cytotoxic T cell infiltration in close proximity to tumour cells, whereas non-responders showed enrichment of immunosuppressive, TGF-β and angiogenic signatures. In peripheral blood post-treatment, responders developed a proliferative burst of activated CD8(+) T cells and sustained sharing of pre-existing tumour-enriched TCR clones. These findings identify trafficking and maintenance of pre-existing tumour-enriched T cell clones as determinants of response to SABR plus anti-PD-1 in ccRCC.
- Department(s)
- Laboratory Research; Radiation Oncology; Biostatistics and Clinical Trials; Medical Oncology; Surgical Oncology
- Publisher's Version
- https://doi.org/10.1038/s41467-026-74255-x
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-026-74255-x- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-08-06 02:27:26
Last Modified: 2026-08-06 02:27:32