Tetramer-aided sorting and single-cell RNA sequencing facilitate transcriptional profiling of antigen-specific CD8+ T cells

•Peptide-MHC tetramer-aided FACS-sorted human CMV pp65 antigen-specific CD8+ T was used as a model for transcriptional profiling of antigen-specific CD8+ T cells at single cell level.•Use of tetramer during FACS sorting did not alter the transcriptional profile or clonal distribution of pp65-specific CD8+ T cells.•An antigen-specific response (ASR) gene signature was derived from the tetrameractivated pp65-specific CD8+ T cell clones.•ASR signature in pretreatment tumor samples was predictive of improved progression free survival in non-small cell lung cancer patients treated with anti-PDL1, anti-VEGF and chemotherapy combination.•The ASR signature could be valuable for predicting responses to checkpoint blockade in other cancer indications and may potentially facilitate development of a diagnostic tool to select patients that are more likely to respond to immunotherapy.