The degree of T-cell infiltration has been suggested as an important prognostic biomarker for colorectal cancer (CRC) patients, regardless of other clinical and/or pathological factors. In this study, we analyzed tumor-infiltrating lymphocyte (TIL) counts of CRC using Lunit SCOPE IO, an artificial intelligence (AI)-powered whole slide image (WSI) software analyzer. Our aim was to analyze the prognostic significance of AI-powered TIL analysis in CRC.
Lunit SCOPE IO was trained and validated with a 2.8 x 109 micrometer2 area and 5.9 x 106 TILs from 3,166 H&E Whole-Slide Images (WSI) of multiple cancer types, annotated by 52 board-certified pathologists. The Inflamed Score (IS) was defined as the proportion of all tumor-containing 1 mm2-size tiles within a WSI classified as being of the inflamed immune phenotype (high TIL density within cancer epithelium). H&E images, sequencing data and survival data of stage I-III CRC patients from The Cancer Genome Atlas (TCGA) were utilized for this analysis.
Stage I-III CRC samples (n = 461) with clinical data were analyzed. The median of IS was 8.56 (IQR 3.74-18.39). IS showed moderate positive correlations with CD8A (rs = 0.422, p < 0.001) and CD3G (rs = 0.377, p < 0.001) expression levels but weaker positive correlations with regulatory T cells (rs = 0.162, p < 0.001), TH1 (rs = 0.209, p < 0.001) or TH2 cell proportions (rs = 0.128, p = 0.006). The IS was higher in CMS1 group compared to CMS 2-4 groups (median 18.49 vs. 6.90, p < 0.001). No significant differences in IS was observed across TNM stages. The recurrence-free survival of the patients with IS higher than third quartile (>= 18.39) were significantly longer compared to the lower group (p = 0.034, HR 0.540, 95% CI 0.306-0.954). The same outcome was observed in cases with MSS tumors (p = 0.023, HR 0.380, 95% CI 0.165-0.877).
AI-powered analysis of WSI can provide prognostic information in stage I-III CRC patients. Further development of AI-powered TIL analysis including the spatial information of TIL in relation to tumor cells may improve prognostic power.
Clinical trial identification
Legal entity responsible for the study
Y. Lim: S. Song; S. Ahn; J. Ryu; H. Song; M. Ma; S. Park; S. Pereira; B.J. Aum; S. Shin; S. Cho; K. Paeng; D. Yoo; W. Jung; C. Ock: Financial Interests, Personal, Full or part-time Employment: Lunit Inc. All other authors have declared no conflicts of interest.