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

ABSTRACT: Analysing and comparing the counts and ratios of specific T-cell subsets in and between primary colorectal cancer (pCRC) and adjacent non-tumor mucosa (NM) may reveal distinct prognostic value in patients who already have liver metastases (LM) and those who develop them later. Formalin-fixed paraffin-embedded specimens of pCRC and NM were collected retrospectively from stage IV patients (n=55) with synchronous LM, and stage I-III patients (n=44) who developed metachronous LM later. CD3⁺, CD8⁺, CD45RO⁺, CD4⁺, and Foxp3⁺ T-cells were stained immunohistochemically and quantified in NM and the tumor center (TC) of pCRC. T-cell densities in NM and TC as well as their ratios (TC/NM) were tested as prognostic variables for overall survival (OS). Foxp3⁺/CD8⁺, Foxp3⁺/CD4⁺ and CD4⁺/CD8⁺ ratios were also evaluated for their prognostic relevance. Cell densities in TC and NM of stage I-III patients were also tested for associations with the time to occurrence of liver metastases. 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 patients, high densities of Foxp3⁺ cells, high Foxp3⁺/CD4⁺ and Foxp3⁺/CD8⁺ cell ratios in the NM, and high CD4⁺ cell densities in the TC were associated with longer OS. Stage I-III patients with a high CD4⁺/CD8⁺ cell ratio in the NM had longer OS whereas a high Foxp3⁺/CD8⁺ cell ratio in the TC was associated with a significantly shorter time to the occurrence of LM. High CD4⁺ cell densities in the TC, high Foxp3⁺/CD4⁺ and Foxp3⁺/CD8⁺ cell ratios in the NM retained significant associations with OS in all multivariable models. 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 predominating in the NM regardless of the metastasis status. Additionally, the assessment of T-cells in the NM and pCRC, both individually and in ratios, may help predict survival in CRC patients and the time to occurrence of LM in stages I-III.

SUBMITTER: Andriy Trailin 

PROVIDER: S-BIAD2384 | bioimages |

REPOSITORIES: bioimages