Prognostic Value of CD8+ T Cells at the Invasive Margin Is Comparable to the Immune Score in Nonmetastatic Colorectal Cancer: A Prospective Multicentric Cohort Study

Abstract

Purpose: The Immunoscore predicts colorectal cancer prognosis but faces adoption barriers because of complex software and reimbursement issues. This study used open-source methods to explore a simplified prognostic model in nonmetastatic colorectal cancer by focusing on single T-cell markers.

Experimental design: A multicentric prospective cohort study in patients with nonmetastatic colorectal cancer assessed CD3+ and CD8+ tumor-infiltrating lymphocytes (TIL) in the invasive margin (IM) and tumor core (TC) using QuPath. An immune cell score (ICS), based on TIL densities (CD3-IM, CD8-IM, CD3-TC, and CD8-TC), was calculated similarly to the Immunoscore. A split sample approach (70:30) estimated adjusted HRs for cancer-specific survival in training and validation sets. Classification and regression tree analysis identified the most prognostic TIL, and its model was compared with an ICS model for performance (Brier score) and discrimination (concordance probability estimate).

Results: Over a median follow-up of 9.0 years, 203 colorectal cancer-specific deaths occurred among 1,260 patients. Classification and regression tree-selected CD8-IM was the most prognostic TIL at a cutoff of 231 cells/mm2. Patients with high CD8-IM had better cancer-specific survival than low CD8-IM in both training (HR 0.58, 95% confidence interval, 0.40-0.84) and validation sets (HR 0.35, 95% confidence interval, 0.21-0.60). Brier scores of CD8-IM and ICS survival models were comparable in both training and validation cohorts, whereas the survival discrimination of CD8-IM slightly outperformed the ICS in the validation set (concordance probability estimate: CD8-IM: 0.748; ICS: 0.730).

Conclusions: CD8-IM alone provided prognostic information comparable with the ICS. Simplified, cost-effective TIL assessments could improve clinical translation and guide adjuvant therapy in early-stage colorectal cancer.