Divergent transcriptional states and kinetics of circulating tumor-infiltrating lymphocyte repertoires with highly homologous T-cell receptor sequences in a patient during immunotherapy.

ABSTRACT: Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy. We found frequent circulating CD8⁺ TIL-TCRs with identical complementarity determining region 3 (CDR3)α amino acid sequences but

SUBMITTER: Kajihara R 

PROVIDER: S-EPMC11784231 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature