Computational image features of immune architecture reveal molecular patterns associated with outcome and risk of recurrence in microsatellite-stable or MSI-low colon cancers
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Updated: Nov 2, 2026
Multiplex Immunofluorescence Combined with Spatial Image Analysis for the Clinical and Biological Assessment of the Tumor Microenvironment
Published on: June 2, 2023
Bolin Song1, Himanshu Maurya1, Sirvan Khalighi2
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States.
Background:
Tumor-infiltrating lymphocyte (TIL) density provides prognostic information in colon adenocarcinoma (COAD), but the additional value of TIL spatial organization remains unclear.
Methods:
We developed CoATIL, a computational pathology framework quantifying TIL spatial architecture from routine H&E-stained whole-slide images. The study included 461 patients with microsatellite-stable or MSI-low COAD. The model was trained using 140 patients from University Hospitals Cleveland Medical Center, validated internally in 52 patients, and externally in The Cancer Genome Atlas (n = 130), and Guangdong Provincial People's Hospital (n = 139). Prognostic performance was assessed using Kaplan-Meier analysis and multivariable Cox regression. CoATIL was compared with a clinical model and eight foundation-model-based multiple-instance learning approaches.
Results:
CoATIL was associated with progression-free survival (HR per standard-deviation increase, 1.32; 95% CI 1.13-1.55; p < 0.001; C-index=0.66) and remained prognostic after adjustment for clinicopathologic factors in each validation cohort (adjusted HRs, 2.00-4.40; all p < 0.05). High-versus-low-risk stratification was retained within stage II (HR 3.07; 95% CI 1.83-5.15; p < 0.001) and stage III disease (HR 3.24; 95% CI 1.28-8.19; p = 0.013). The combined clinical-CoATIL model achieved a higher C-index than the clinical model alone (0.69 versus 0.61; paired bootstrap difference, 0.08; 95% CI 0.03-0.14). Exploratory genomic analyses associated AMER1 and FBXW7 mutations with lower and higher CoATIL risk scores, respectively.
Conclusions:
Spatial immune architecture extracted from routine histology provides complementary prognostic information in COAD. Prospective validation is warranted.