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

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This article discusses the utilization of single-cell RNA+TCR sequencing (scRNA+TCR seq) to explore the antitumor response of tumor-infiltrating T lymphocytes in the tumor microenvironment of non-small cell lung cancer patients. The study revealed the presence of dual TCR T cells with distinct characteristics, including clonal hyperplasia and tissue residency preferences. Dual TCR CD8+T cells were found to display potent antitumor activity, while dual TCR CD4+T cells showed a more even distribution across tissues. The use of scRNA+TCR seq and advanced technologies offers new insights into the regulation of dual TCR T cell responses in the TME, opening up avenues for further research.

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.

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