scRNA+ TCR-seq revealed dual TCR T cells antitumor response in the TME of NSCLC.

The intricate origins, subsets, and characteristics of TCR (T Cell Receptor) s, along with the mechanisms underpinning the antitumor response of tumor-infiltrating T lymphocytes within the tumor microenvironment (TME) remain enigmatic. Recently, the advent of single-cell RNA+TCR-sequencing (scRNA+TCR seq) has revolutionized TME analysis, providing unprecedented insight into the origins, cell subsets, TCR CDR3 compositions, and the expression patterns of response/depletion factors within individual tumor-infiltrating T lymphocytes. Our analysis of the shared scRNA+TCR seq dataset revealed a substantial presence of dual TCR T cells, characterized by clonal hyperplasia and remarkable migratory prowess across various tissues, including blood, normal, peritumoral, and tumor tissues in non-small cell lung cancer patients. Notably, dual TCR CD8+T cells predominantly fell within the CXCL13+subset, displaying potent antitumor activity and a strong preference for tumor tissue residency. Conversely, dual TCR CD4+T cells were predominantly classified as CD5+ or LMNA+subsets, exhibiting a more even distribution across diverse tissue types. By harnessing scRNA+TCR seq and other cutting-edge technologies, we can delve deeper into the effects and mechanisms that regulate the antitumor response or tolerance of dual TCR T cells. This innovative approach holds immense promise in offering fresh perspectives and avenues for advancing research on TIL (Tumor infiltrating lymphocyte)s within the TME.