Deep-learning enabled combined measurement of tumour cell density and tumour infiltrating lymphocyte density as a prognostic biomarker in colorectal cancer

BACKGROUND: Within the colorectal cancer (CRC) tumour microenvironment, tumour infiltrating lymphocytes (TILs) and tumour cell density (TCD) are recognised prognostic markers. Measurement of TILs and TCD using deep-learning (DL) on haematoxylin and eosin (HE) whole slide images (WSIs) could aid management. METHODS: HE WSIs from the primary tumours of 127 CRC patients were included. DL was used to quantify TILs across different regions of the tumour and TCD at the luminal surface. The relationship between TILs, TCD, and cancer-specific survival was analysed. RESULTS: Median TIL density was higher at the invasive margin than the luminal surface (963 vs 795 TILs/mm , P = 0.010). TILs and TCD were independently prognostic in multivariate analyses (HR 4.28, 95% CI 1.87-11.71, P = 0.004; HR 2.72, 95% CI 1.19-6.17, P = 0.017, respectively). Patients with both low TCD and low TILs had the poorest survival (HR 10.0, 95% CI 2.51-39.78, P = 0.001), when compared to those with a high TCD and TILs score. CONCLUSIONS: DL derived TIL and TCD score were independently prognostic in CRC. Patients with low TILs and TCD are at the highest risk of cancer-specific death. DL quantification of TILs and TCD could be used in combination alongside other validated prognostic biomarkers in routine clinical practice.