Prognostic and predictive value of tumor infiltrating lymphocytes in combination with systemic inflammatory markers in colon cancer

Abstract

Objective: Systemic inflammatory indices and CD8(+) tumor infiltrating lymphocytes (TILs) in the tumor microenvironment are highly prognostic in colon cancer (CC) but combined assessment is less well studied. The purpose of this study was to investigate the prognostic and predictive value of CD8(+) TILs in combination with systemic inflammatory indices in patients with resected stage II-III colon cancer.

Patients and methods: Patients with stage II-III CC (n = 304) diagnosed between 2008 and 2016 were included. Pan-immune inflammation value (PIV) was used as a comprehensive inflammatory index and was calculated as: [neutrophil count × platelet count × monocyte count]/lymphocyte count. The mean density of CD8+ TILs in the periphery and center of the tumor was assessed and dichotomized at the 75th percentile. Combined inflammation score (CIS) was classified as "high" in patients with high PIV (>median) plus low mean CD8(+) TILs density, and CIS "low" in the remaining patients.

Results: 5-year DFS was 71% (78% in stage II, 63.4% in stage III). PIV was higher in right colon tumors, T4 tumors and in patients with obstruction / perforation. CD8(+) TIL density was lower in node positive tumors. High PIV and low CD8(+) TILs were associated with shorter disease-free survival (DFS). In multivariate analysis; age > 65 years, stage III disease and high CIS (PIV^high / CD8^low) were associated with shorter DFS. Among patients with stage II disease, patients with high CIS (PIV^high / CD8^low) derived significant benefit from adjuvant chemotherapy while those with low CIS derived no benefit.

Conclusion: Combined inflammation score may represent a new prognostic factor for localized colon cancer and predictor of chemotherapy response in patients with stage II disease.

Keywords: CD8 infiltration, prognosis; Colon cancer; Systemic inflammation.