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

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.