The immunological characterization of expanded tumor-infiltrating lymphocytes in renal cell carcinoma patients

ABSTRACT: In this study, we comprehensively characterized the non-expanded and expanded tumor-infiltrating lymphocytes (TILs) from treatment-naïve RCC patients, as well as the corresponding “young†TILs (pre-REP TILs) and “rapidly expanded†TILs (REP TILs) following a clinical-grade TIL production protocol. From our scRNA+TCRαβ-seq and TCRβ-seq analyses, we show that the REP protocol preferentially favors the expansion CD4+ T-cells that originate from small T-cell clones in the tumor microenvironment (TME), indicating that the large, exhausted T-cell clones in the tumor do not expand during the protocol. We further identified RCC-associated TCR motifs that were validated in multiple TCRαβ-seq and scRNA+TCRαβ-seq datasets, as well as quantified the RCC-associated TCRs from the REP protocol. Overall, the T-cells carrying the RCC-associated TCRs remained high in the tumors and corresponding pre-REP TILs, but the frequency was reduced in the REP TILs. Furthermore, the overall anti-viral TCRs remained low throughout the REP protocol. Our results provide an in-depth understanding of the origin, phenotype, and specificity of the TCRs in RCC TILs.

PROVIDER: EGAS00001006952 | EGA |

REPOSITORIES: EGA