Dynamic immune profiling predicts response to radiation plus anti-PD-1 therapy in oligometastatic renal cell carcinoma

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&#39;Souza, C; Neeson, PJ; Siva, S

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;
Details: Publication Year 2026-07-08,Volume 17,Issue #1,Page 8453
Journal Title: Nature Communications
Publication Type: Research article
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.
Publisher: Springer Nature
Keywords: Humans; *Carcinoma, Renal Cell/immunology/therapy/mortality/pathology; *Kidney Neoplasms/immunology/therapy/pathology/mortality; Antibodies, Monoclonal, Humanized/therapeutic use; Female; *Radiosurgery; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology; Male; Middle Aged; Prospective Studies; Aged; CD8-Positive T-Lymphocytes/immunology; *Immune Checkpoint Inhibitors/therapeutic use; Combined Modality Therapy; Treatment Outcome; T-Lymphocytes, Cytotoxic/immunology
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: 2026-09-16 04:38:37