{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:01:38Z","timestamp":1780038098534,"version":"3.53.1"},"reference-count":147,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colorectal cancer (CRC) continues to exhibit a high rate of both incidence and mortality, and most patients respond limitedly to immunotherapy. Increasing evidence suggests that tumor progression is governed by complex interactions between tumor cells (TCs) and the immune microenvironment. However, the multi-layered regulatory mechanisms underlying these interactions remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing profiles sourced from GEO were merged for subsequent integrative analysis. Leveraging Seurat, we carried out data quality filtering, dimensionality reduction, clustering, and cell annotation, while Harmony was applied to correct batch effects. Malignant cells were identified using inferCNV. Functional characteristics were analyzed using various enrichment analyses, and pseudotime analysis was conducted using CytoTRACE, Monocle, and Slingshot. Communication between cells and transcriptional regulatory circuitry were constructed using CellChat and SCENIC. The critical factor\n                      <jats:italic>TRIM31<\/jats:italic>\n                      was confirmed through\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments. Furthermore, prognostic models were constructed based on TCGA data, and analyses of immune infiltration and drug sensitivity were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The TCs were further classified into six subtypes, among which C4\n                      <jats:italic>\n                        TRIM31\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      TCs were enriched in tumor tissues, exhibited an immune-related phenotype, and showed significant enrichment in hallmark pathways. Integrative analysis suggested potential crosstalk between these cells and macrophages via MIF and GALECTIN signaling pathways. Silencing\n                      <jats:italic>TRIM31<\/jats:italic>\n                      significantly reduced the proliferative and invasive capacities of CRC cells. Moreover, the\n                      <jats:italic>\n                        TRIM31\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      TCs risk group model constructed based on C4\n                      <jats:italic>\n                        TRIM31\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      TCs demonstrated effective prognostic stratification, especially for the high-risk group displayed enhanced immunosuppression and differential drug sensitivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Overall, we characterized a comprehensive cancer-immune regulatory landscape involving transcriptional programs, intercellular crosstalk, and tumor evolution dynamics. Within this context, a distinct subtype of C4\n                      <jats:italic>\n                        TRIM31\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      TCs exhibiting immunoregulatory features was characterized, suggesting their involvement in shaping the cancer immunity landscape of CRC. Collectively, these results established a foundation for the identification of immune-associated biomarkers and offered insights into the prediction of immunotherapeutic efficacy and resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1848654","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:03:02Z","timestamp":1780034582000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative single-cell analysis reveals TRIM31+ colorectal tumor cells orchestrating macrophage crosstalk within the cancer-immunity regulome"],"prefix":"10.3389","volume":"17","author":[{"given":"Yunxuan","family":"Shi","sequence":"first","affiliation":[{"name":"College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, 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