Tumor containment by immune cells and fibrotic capsule improve survival of patients following resection of colorectal liver metastasis

Background & Aims: Liver metastases occur in 40 – 50% of patients with colorectal cancer and determine longterm survival. The aim of this study was to examine the immunologic architecture of colorectal liver metastasis and its impact on patient survival.

Methods: 222 colorectal liver metastases were stained for H&E, masson trichrome, and alpha smooth muscle actin. Further, immunohistochemical stainings were analysed for CD4+, CD45RO+ and CD8+ cell numbers separately for tumor, infiltrative margin and distant liver stroma. These findings were correlated with clinical data and patient outcome.

Results: Tumor containment by fibrotic capsule formation around the liver metastasis, was a prognostic parameter for patient survival (P < 0.0001) and independently lead to higher R0-resection rates (P = 0.03). Dense infiltration of CD4+, CD45RO+ and CD8+ cells at the infiltrative margin correlated with increased patient survival (P = 0.0002; P < 0.0001; P = 0.0098). In particular, localized cell infiltration at the infiltrative margin with low cell infiltration in the distant liver stroma, expressed by a ratio of CD4+, CD45RO+ and CD8+ cells > 2, prolonged patient survival time (P < 0.0001; P = 0.0002; P < 0.0001). Using these factors, a cellular immune score was designed that stratifies patient survival (P < 0.0001).

Conclusions: Fibrotic capsule formation and localized cell infiltration of colorectal liver metastasis by CD4+, CD45RO+ and CD8+ cells prolong patient survival. Based on these immunologic criteria we developed a cellular immune score to stratify patients according to prognosis which potentially extends the immune scoring classification planned for primary colorectal carcinomas to patients with colorectal liver metastasis.