AI-powered immune profiling from histopathology slides for chemo-radiotherapy outcome prediction in rectal cancer: a study using clinical trial and real-world cohorts.
retrospective_cohort · Level III
Where this comes from
- Record sourced from PubMed, PMID 41253645.
- Also identified by DOI 10.1016/j.ebiom.2025.105993 and PMC identifier 12790592.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The impact of the tumour-immune microenvironment on locally advanced rectal cancer (LARC) outcomes remains unclear. This study quantitatively assesses the synergistic influence of tumour-infiltrating lymphocytes (TILs), tumour-associated macrophages (TAMs), mitotic activity, and DNA mutations in predicting outcomes for LARC patients undergoing neoadjuvant chemo-radiotherapy (nCRT). Three cohorts (ARISTOTLE-RC, UCLH-RC, TCGA-CRC) were stratified by densities of AI-quantified TILs, TAMs, and mitotic figures with cut-offs identified on a hold-out subset and integrated with DNA mutations to assess correlations with disease-free survival (DFS) and overall survival (OS). Immune cell dynamics pre- and post-CRT were also evaluated. In ARISTOTLE-RC, TIL<sup>+</sup> patients had significantly improved DFS (HR = 0.59, 95% CI: 0.39-0.90, p = 0.013) and OS (HR = 0.42, 95% CI: 0.24-0.73, p < 0.005), while TAM<sup>+</sup> was associated with shorter DFS (HR = 1.65, 95% CI: 1.00-2.72, p = 0.045). Similar patterns were observed in UCLH-RC and TCGA-CRC. TIL<sup>+</sup>/KRAS<sup>-</sup> patients had significantly improved DFS (HR = 0.41, 95% CI: 0.22-0.75, p < 0.005) and OS (HR = 0.28, 95% CI: 0.13-0.62, p < 0.005). In TP53-mutated patients, TAM<sup>+</sup> group showed shorter DFS (HR = 1.46, 95% CI: 1.07-2.01, p = 0.0151), while among TP53-wild-type patients, no difference in DFS (HR = 1.00, 95% CI: 0.66-1.52, p = 0.9930) was observed between the two subgroups. Patients who transitioned after nCRT from TIL<sup>-</sup> to TIL<sup>+</sup> had improved DFS (HR = 0.70, 95% CI: 0.50-0.97, p = 0.028) and exhibited a significantly higher pre-treatment mitotic index (mean difference = 9.36, 95% CI: 1.87-16.85, p = 0.0385). These findings suggest the potential utility of AI-driven immune profiling for clinical decision-making in LARC patients undergoing nCRT. Cancer Research UK (RRNPSF-Jan21/100001, A18745, C7893/A2899), UK Research and Innovation (MR/T040785/1).
Medical subject headings
- Rectal Neoplasms