BACKGROUND: Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomic profiling of the systemic T cell response following SABR, with or without preceding immunotherapy/chemotherapy. METHODS: We conducted single-cell RNA and T cell receptor (TCR) sequencing of T cells from peripheral blood of seven patients with early-stage NSCLC taken pre- and post-SABR without or with prior immunotherapy and chemotherapy (icSABR). Other flow cytometry, single-cell RNA-seq data and bulk RNA-seq data were used to validate the results. RESULTS: We uncovered distinct T cell response patterns induced by these treatments: while terminal effector CD8 CONCLUSIONS: These findings reveal a complex interplay between SABR and immunotherapy, with potentially valuable implications for treatment strategies involving SABR and immunotherapy to induce systemic T cell responses for tumor eradication in patients with NSCLC.