Radiation, Immunotherapy, and T-cell reinvigoration: Dynamic Immune Profiling Predicts Response to SABR/Anti-PD-1 therapy in Oligometastatic Renal Cell Carcinoma [TCR-Seq]

We report for the first time observations from longitudinal immune monitoring in patients with oligometastatic ccRCC receiving combined radiation and immunotherapy. Transcriptomic and multiplex immunohistochemistry analyses revealed responders had significantly increased infiltrating cytotoxic T-cells in close proximity to the tumour cells. In contrast, non-responders exhibited elevated immunosuppressive gene signatures associated with tumour angiogenesis and transforming growth factor beta (TGF-β) signalling. Responders also exhibited greater richness in T cell receptor (TCR) repertoire pretreatment in the tumour. Serial blood analysis revealed that a proliferative burst of activated, cytotoxic T cell subsets in the peripheral blood correlated with treatment response. Furthermore, responders showed increased sharing of pre-existing expanded TCR clones from the tumour tissue with the peripheral circulation post-treatment, suggesting active trafficking of anti-tumour T cells. These findings highlight pre-existing local and systemic immune profiles and the magnitude of circulating T cell reinvigoration as critical determinants of treatment response to combined SABR, and anti-PD-1 therapy in oligometastatic ccRCC.