Abstract 2457: Prognostic value of CD8+ T-cells at the invasive margin is comparable to immune score in non-metastatic colorectal cancer: A prospective multicentric cohort study

Abstract Background: Immunoscore predicts colorectal cancer prognosis but faces adoption barriers due to complex software and reimbursement issues. This study used open-source methods to explore a simplified prognostic model in non-metastatic CRC by focusing on single T-cell markers. Methods: A multicentric prospective cohort study in non-metastatic CRC patients assessed CD3+ and CD8+ tumor infiltrating lymphocytes (TILs) in the invasive margin (IM) and tumor core (TC) using QuPath. An immune cell score, based on TIL densities (CD3-IM, CD8-IM, CD3-TC, CD8-TC), was calculated similarly to the Immunoscore®. A split sample approach (70:30) estimated adjusted hazard ratios for cancer-specific survival (CSS) in training and validation sets. CART analysis identified the most prognostic TIL, and its model was compared to an immune cell score model for performance (Brier score) and discrimination (Concordance Probability Estimate, CPE). Results: Over a median follow-up of 9.0 years, 203 CRC-specific deaths occurred among 1, 260 patients. CART-selected CD8-IM was the most prognostic TIL at a cut-off of 231 cells/mm2. Patients with CD8-IMHi had better CSS than CD8-IMLow in both training (HR 0.58, 95% CI 0.40-0.84) and validation sets (HR 0.35, 95% CI 0.21-0.60). Brier scores of CD-8IM and immune cell score survival models were comparable in both training and validation cohort, whereas the survival discrimination of CD8-IM slightly outperformed the immune cell score in the validation set (CPE: CD8-IM 0.748, IS 0.730). Conclusion: CD8-IM alone provided prognostic information comparable to the immune cell score. Simplified, cost-effective TIL assessments could improve clinical translation and guide adjuvant therapy in early-stage CRC. Citation Format: Durgesh Wankhede, Niels Halama, Matthias Kloor, Dominic Edelmann, Hermann Brenner, Michael Hoffmeister. Prognostic value of CD8+ T-cells at the invasive margin is comparable to immune score in non-metastatic colorectal cancer: A prospective multicentric cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2457.