Single-cell transcriptome analysis reveals gene signatures associated with T-cell persistence following adoptive cell therapy

A patient (4095) with metastatic colorectal cancer was treated with polyclonal tumor infiltrating lymphocytes (TILs) targeting the KRAS(G12D) hotspot mutation. Three dominant clonotypes specifically recognizing KRAS(G12D) epitopes were identified, but we found that only two clonotypes persisted 40 days after TIL treatment. Because of these findings, in this study, we utilized a 10X system to perform single-cell TCR/transcriptome analysis for the TILs isolated from this patient, together with 4 additional TILs isolated from 4 patients (4007, 4069, 4071, 4081) treated within 5-month window. In addition, we performed single-cell TCR/transcriptome analysis on Patient 4095's peripheral blood lymphocytes (PBL) day 12 or day 40 after TIL treatment. We also utilized a low-throughput Fluidigm C1 system to perform single-cell RNA-Seq on TIL4095. Please use accession number GSE136610 to find the dataset. Single-cell TCR/transcriptome analysis on tumor infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBL) was perform on a 10X Chromium instrument using single-cell VDJ kits