ArticleCancer medicine2026
Foxp3+/CD4+ Cell Ratio in Primary Colorectal Cancer Predicts Opposite Prognoses Following Resection of Synchronous or Metachronous Liver Metastases.
Article in Cancer medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundWe aimed to assess the abundance, distribution, and prognostic significance of Foxp3+ and CD4+ T-cells and their ratio in primary colorectal cancer (pCRC) and liver metastases (LM) in patients with synchronous and metachronous disease.
methodsWe performed a retrospective study involving patients who underwent resections of both pCRC and either synchronous (N = 55) or metachronous LM (N = 44). Following sequential immunohistochemical staining for CD4+ and Foxp3+ T-cells, whole-slide scans were analyzed using QuPath software to quantify T-cells in the tumor center (TC), inner margin (IM), outer margin (OM), and peritumor zone (PT) of both pCRC and LM. T-cell densities and their ratios were tested as prognostic variables for disease-free survival (DFS) and time to recurrence (TTR).
resultsWe found greater densities of CD4+ cells in OM and PT of LM of synchronous and metachronous patients compared to pCRC. In both groups, densities of Foxp3+ cells were higher in all regions of interest of pCRC compared to LM. CD4+ cells were more abundant than Foxp3+ cells in IM, OM, and PT of LM; densities of Foxp3+ cells were higher in TC and IM of pCRC. Neither CD4+ nor Foxp3+ cells in pCRC were individually predictive of survival, but a higher Foxp3+/CD4+ cells ratio in OM of pCRC in the metachronous group was associated with shorter DFS (hazard ratio (HR): 2.34, 95% confidence interval (CI): 1.14-4.79, p = 0.02) and TTR. Conversely, in OM and PT of pCRC in the synchronous group, a higher ratio was associated with longer DFS (HR: 0.53, CI: 0.29-0.98, p = 0.04 and HR: 0.46, CI: 0.25-0.86, p = 0.02, respectively) and TTR.
conclusionsThe high Foxp3+/CD4+ cells ratio was associated with shorter survival in metachronous and longer survival in synchronous disease, providing novel clinical implications. Foxp3+/CD4+ cells ratio in pCRC may help better stratify CRC patients with synchronous LM after resection of the primary tumor.
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