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<p>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<sup>+</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月8日

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  • Van To,
  • Niko Thio,
  • Rebecca Castle,
  • Sean Macdonald,
  • Tristan Molden-Hauer,
  • James Wells,
  • Ryan McMahon,
  • Mathias Bressel,
  • Ben Tran,
  • Arun A. Azad,
  • Daniel Moon,
  • Sree Appu,
  • Lih-Ming Wong,
  • Declan G. Murphy,
  • Katharine Cuff,
  • David Pryor,
  • Lavinia Spain,
  • Lewis Au,
  • Criselle D’Souza,
  • Paul J. Neeson,
  • Shankar Siva

摘要

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.