Immunological nomograms predicting prognosis and guiding adjuvant chemotherapy in stage II colorectal cancer

BACKGROUND: The type, abundance, and location of tumor-infiltrating lymphocytes (TILs) have been associated with prognosis in colorectal cancer (CRC). This study was conducted to assess the prognostic role of TILs and develop a nomogram for accurate prognostication of stage II CRC. METHODS: Immunohistochemistry was conducted to assess the densities of intraepithelial and stromal CD3+, CD8+, CD45RO+, and FOXP3+ TILs, and to estimate PD-L1 expression in tumor cells for 168 patients with stage II CRC. The prognostic roles of these features were evaluated using COX regression model, and nomograms were established to stratify patients into low- and high-risk groups and compare the benefit from adjuvant chemotherapy. RESULTS: In univariate analysis, patients with high intraepithelial or stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs were associated significantly with better relapse-free survival (RFS) and overall survival (OS), except for stromal CD45RO+ TILs. In multivariate analysis, patients with high intraepithelial CD3+ and stromal FOXP3+ TILs were associated with better RFS (p<0.001 and p=0.032, respectively), while only stromal FOXP3+ TILs was an independent prognostic factor for OS (p=0.031). The nomograms were well calibrated and showed a c-index of 0.751 and 0.757 for RFS and OS, respectively. After stratifying into low- and high-risk groups, the high-risk group exhibited a better OS from adjuvant chemotherapy (3-year OS of 81.9% vs 34.3%, p=0.006). CONCLUSION: These results may help improve the prognostication of stage II CRC and identify a high-risk subset of patients who appeared to benefit from adjuvant chemotherapy.