Tumor-infiltrating cytotoxic T-cells predict outcome in colorectal carcinoma, clinical stadium II

PURPOSE: Simple methods to identify colorectal cancer (CRC) patients in clinical stadium II (T3-4N0M0, Dukes‘ B) at high risk of recurrence are needed. Tumor–infiltrating lymphocytes (TILs) are a possible prognostic factor, cytotoxic TILs (CD8+ cells) are generally considered as prognostically favorable, whereas a subgroup of TILs, regulatory T-cells ( T-reg, CD4+ CD25+ FOXP3 +) are not. We have evaluated the effect of the presence of intraepithelial CD8+ cells on overall survival in patients with CRC in clinical stadium II.

METHODS: Formalin-fixed, paraffin embedded tumor samples from 13 patients with CRC in clinical stadium II were evaluated by im-munohistochemistry using commercially available anti-CD8 mouse monoclonal antibody. Intraepithelial CD8+ cells were enumerated in one high power magnification field in the area with the highest CD8+ cell infiltration. Its prognostic effect was evaluated using Kaplan-Mayer method. Moreover, preoperative, total white cells and individual counts of eosinophiles, neutrophiles, lymphocytes were evaluated from peripheral blood as well.

RESULTS: We divided the patients into two groups according to the number of intraepithelial CD8+ T-cells, as quantified in the most abundant areas, so called “hot spots”. First group with 0 to 2 CD8+ cells and the second group with more than 2 CD8+ cells. The median observation period was 50 months. The number of intraepithelial CD8+ T-cells correlated with patients‘ longer overall survival (poor prognosis for the patients in the first group with less CD8+ cells). CONCLUSION: We conclude that infiltration of CD8+ cells might be an important prognostic factor in CRC in clinical stage II. Knowledge of local immune responses is important for the development of therapeutic strategies. To support our pilot study there are futher experimets undergoing in our laboratory.

ACKNOWLEDGMETS: This project is supported by IGA MZ CR NR/9076-4.