Low Infiltration of Peritumoral Regulatory T Cells Predicts Worse Outcome Following Resection of Colorectal Liver Metastases

The tumor-infiltrating lymphocyte (TIL) count in several types of cancer, including colorectal cancer and colorectal liver metastases (CRLM), reportedly predicts survival following resection; however, the prognostic significance of the TIL counts remains controversial. In total, 162 patients who underwent potentially curative resection for CRLM from 1992 to 2010 were immunohistochemically analyzed retrospectively. CD4, CD8, and FoxP3 were examined as markers for helper T cells, cytotoxic T cells, and regulatory T cells (Tregs), respectively. The correlation between patients' TIL composition and long-term outcome was investigated. The median follow-up time was 46.6 months for all patients and 46.8 months for survivors. Cancer-specific survival (CSS) at 1, 3, and 5 years was 93.2, 65.6, and 51.0 %, respectively. The 5-year disease-free survival and CSS among patients with high infiltration of peritumoral Tregs was 44.2 and 74.8 %, respectively, while those of patients with low infiltration of peritumoral Tregs was 18.9 and 40.3 %, respectively (p < 0.01 for both). Multivariate analyses indicated that synchronous liver metastases, hypoalbuminemia, and low peritumoral Treg infiltration were significant predictors of unfavorable CSS. Low peritumoral Treg infiltration proved to be a significant predictor of unfavorable CSS in patients undergoing resection for CRLM.