Background We proposed an artificial intelligence-based immune index, Deep-immune score, quantifying the infiltration of immune cells interacting with the tumor stroma in hematoxylin and eosin-stained whole-slide images of colorectal cancer. Methods A total of 1010 colorectal cancer patients from three centers were enrolled in this retrospective study, divided into a primary (N = 544) and a validation cohort (N = 466). We proposed the Deep-immune score, which reflected both tumor stroma proportion and the infiltration of immune cells in the stroma region. We further analyzed the correlation between the score and CD3+ T cells density in the stroma region using immunohistochemistry-stained whole-slide images. Survival analysis was performed using the Cox proportional hazard model, and the endpoint of the event was the overall survival. Result Patients were classified into 4-level score groups (score 1–4). A high Deep-immune score was associated with a high level of CD3+ T cells infiltration in the stroma region. In the primary cohort, survival analysis showed a significant difference in 5-year survival rates between score 4 and score 1 groups: 87.4% vs. 58.2% (Hazard ratio for score 4 vs. score 1 0.27, 95% confidence interval 0.15–0.48, P < 0.001). Similar trends were observed in the validation cohort (89.8% vs. 67.0%; 0.31, 0.15–0.62, < 0.001). Stratified analysis showed that the Deep-immune score could distinguish high-risk and low-risk patients in stage II colorectal cancer (P = 0.018). Conclusion The proposed Deep-immune score quantified by artificial intelligence can reflect the immune status of patients with colorectal cancer and is associate with favorable survival. This digital pathology-based finding might advocate change in risk stratification and consequent precision medicine.

Desmoplastic reaction (DR) is one of many tumor-host interactions and is associated with the overall survival (OS) of patients with colorectal cancer (CRC). However, the clinical significance of DR requires further study in large multicenter cohorts and its predictive value in adjuvant chemotherapy (ACT) response remains unclear. Here, a total of 2225 CRC patients from five independent institutions were divided into primary (N=1012 from two centers) and validation (N=1213 from three centers) cohorts. DR were classified as immature, middle, or mature depending on the presence of myxoid stroma and hyalinized collagen bundles at the invasive front of the primary tumor. OS among different subgroups were compared, and the correlation of DR type with tumor infiltrating lymphocytes (TILs) within stroma, tumor stroma ratio (TSR) and Stroma AReactive Invasion Front Areas (SARIFA) were also analyzed. In the primary cohort, patients with mature DR had the highest 5-year survival rate. These findings were confirmed in validation cohort. Additionally, for stage II CRC, patients classified as non-mature DR would benefit from ACT compared with surgery alone. Furthermore, immature and middle DR were more associated with high TSR, less distribution of TILs within stroma and positive SARIFA compared to mature. Taken together, these data suggest that DR is a robust independent prognostic factor for CRC patients. For stage II CRC patients, non-mature DR could be a potential marker for recognizing high-risk patients who may benefit from ACT.