{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T06:49:23Z","timestamp":1777790963204,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Biol Markers"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Despite treatment advances, prognoses of patients with advanced colorectal cancer remain poor. The limited effectiveness of programmed cell death protein 1 (PD-1) blockade immunotherapy in a subset of patients necessitates a deeper understanding of the colorectal cancer microenvironment. This study aimed to identify new therapeutic targets and potential biomarkers by investigating CD8\u2009\n                      <jats:sup>+<\/jats:sup>\n                      \u2009CD101hiTim3\n                      <jats:sup>+<\/jats:sup>\n                      (CCT) T cells and their progenitors in colorectal cancer, and their association with immunotherapy response at the transcriptomic level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used single-cell sequencing data and The Cancer Genome Atlas database for comprehensive bioinformatics analysis, including single-cell sequencing data analysis, Gene Set Variation Analysis, pseudotime analysis, cell communication analysis, and construction and validation of a prognostic model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Key findings include the identification and annotation of various T-cell subtypes in colorectal cancer, construction of a pseudotime trajectory of CCT T cells and their progenitors showing dynamic gene expression changes, and enhanced interactions between CCT T cell progenitors and other cells in the PD-1 immunotherapy group. We developed and validated a prognostic model comprising 15 gene features with strong prognostic stratification performance, revealing that high-risk patients exhibit transcriptomic associations with potentially reduced responses to immune checkpoint inhibitors (ICIs). Pathway enrichment analysis highlighted critical pathways, including leukocyte adhesion and T cell activation, indicating complex influences on disease progression and treatment responses within the colorectal cancer immune landscape.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study emphasizes the potential importance of targeted therapies that modulate immune interactions and functional states to improve colorectal cancer prognosis, particularly in high-risk patients who show an association at the transcriptomic level with reduced ICI responsiveness.<\/jats:p>\n                  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