Prognostic value of intra-tumoral CD8+/FoxP3+ lymphocyte ratio in patients with resected colorectal cancer liver metastasis

Background and Objectives: Patients with isolated colorectal-cancer-liver-metastases (CRCLM) frequently undergo metastatectomy. Tumor-infiltrating-lymphocytes (TILs) have prognostic potential in the setting of primary colorectal cancer, however, their role in CRCLM is less studied. We aimed to study the spatial distribution and prognostic role of tumor-infiltrating CD8(+) cytotoxic T-cells and FoxP3(+) regulatory T-cells at the metastatic site of CRCLM patients. Methods: TILs were isolated from fresh metastatic tissues of 47 patients with CRCLM. Archived paraffin-embedded tissue, from the same patients, was retrieved. CD8(+) and FoxP3(+) cells, both in the intra-tumoral and the peri-tumoral compartments, were measured by immunohistochemistry on full tissue sections. Proportions of cytotoxic T-cells (CD8(+)) and regulatory T-cells (CD4(+)CD25(+)FoxP3(+)), within CD45(+)TILs, were measured by flow-cytometry. Results: By immunohistochemistry, individual densities of intra-tumoral or peri-tumoral CD8(+) and FoxP3(+) cells were not prognostic of survival. However, the intra-tumoral, but not the peri-tumoral, CD8(+)/FoxP3(+) ratio was an independent predictor of survival (HR 0.43, 95%CI 0.19-0.95, P=0.032). By flow cytometry, the intra-tumoral CD8(+)/regulatory T-cell ratio was also an independent predictor of survival (HR 0.45, 95%CI 0.20-0.99, P=0.044). Conclusions: The ratio of cytotoxic (CD8(+)) to regulatory (FoxP3(+)) T-cells, in the intra-tumoral compartment, but not in the peri-tumoral compartment, can predict survival after resection of CRCLM.