{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:17:27Z","timestamp":1792700247903,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells represent a distinct cellular lineage that emerges during both chronic infections and cancers. Recent studies have shown that persistent antigen exposure can drive the differentiation of precursor exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, termed T\n                    <jats:sub>pex<\/jats:sub>\n                    cells, which are characterized as TCF-1\n                    <jats:sup>+<\/jats:sup>\n                    PD-1\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Elevated T\n                    <jats:sub>pex<\/jats:sub>\n                    cell frequencies in the tumor microenvironment (TME) are associated with improved overall survival (OS) in cancer patients and heightened responsiveness to anti-PD-1 therapy. In our present study, we utilized multi-color immunohistochemistry (mIHC) to determine the localization and clinical implications of tumor-infiltrating T\n                    <jats:sub>pex<\/jats:sub>\n                    cells within the TME of human colorectal cancer (CRC) tissues. We also conducted a multi-omics integrative analysis using single-cell RNA sequencing (scRNA-seq) data derived from both the murine MC38 tumor model and human CRC tissues. This analysis helped delineate the transcriptional and functional attributes of T\n                    <jats:sub>pex<\/jats:sub>\n                    cells within the CRC TME. Furthermore, we employed spatial transcriptome sequencing data from CRC patients to investigate the interactions between T\n                    <jats:sub>pex<\/jats:sub>\n                    cells and other immune cell subsets within the TME. In conclusion, our study not only established a method for T\n                    <jats:sub>pex<\/jats:sub>\n                    cell detection using mIHC technology but also confirmed that assessing T\n                    <jats:sub>pex<\/jats:sub>\n                    cells within the CRC TME could be indicative of patients\u2019 survival. We further uncovered the transcriptional and functional characteristics of T\n                    <jats:sub>pex<\/jats:sub>\n                    cells in the TME and ascertained their pivotal role in the efficacy of immunotherapy against CRC.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2024.1362140","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T23:41:40Z","timestamp":1709682100000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Precursor exhausted CD8+T cells in colorectal cancer tissues associated with patient\u2019s survival and immunotherapy 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