Distribution and prognostic value of T‐cells in primary colorectal cancer and adjacent non‐tumor mucosa in stage IV versus stage I–III patients

Analyzing T-cell subsets in and between primary colorectal cancer (pCRC) and adjacent non-tumor mucosa (NM) may reveal distinct prognostic value in stage IV versus stages I-III patients. Specimens of pCRC and NM were collected retrospectively from stage IV patients (n = 55) with synchronous liver metastases (LM), and stages I-III patients (n = 44) who developed metachronous LM. CD3⁺, CD8⁺, CD45RO⁺, CD4⁺, and Foxp3⁺ T-cells were quantified in NM and the tumor center (TC) of pCRC using immunohistochemistry. T-cell densities in NM and TC and their ratios (TC/NM) were tested as prognostic variables for overall survival (OS), along with Foxp3⁺/CD8⁺, Foxp3⁺/CD4⁺ and CD4⁺/CD8⁺ ratios. In stages I-III, associations with the time to occurrence of LM were also evaluated. In both groups, NM exhibited greater densities of CD3⁺, CD8⁺, CD45RO⁺, and CD4⁺ cells compared to TC, whereas Foxp3⁺ cells were more abundant in the TC. In stage IV, high densities of Foxp3⁺ cells, high Foxp3⁺/CD4⁺ and Foxp3⁺/CD8⁺ ratios in the NM, and high CD4⁺ cell densities in the TC were associated with longer OS. Stages I-III patients with a high CD4⁺/CD8⁺ ratio in the NM had longer OS, whereas a high Foxp3⁺/CD8⁺ ratio in the TC was associated with a shorter time to LM. We revealed a significant difference in the T-cell landscape between pCRC and adjacent NM with Foxp3⁺ cells predominating in the TC and other subsets in the NM. Assessing T-cells and their ratios in both regions may improve prediction of survival in CRC patients and the time to LM in stages I-III.