Immune profiling may improve risk stratification in early-stage colorectal carcinoma

Treatment decisions for pT1 colorectal cancer often rely on traditional histologic features, but these may incompletely predict metastatic risk. We evaluated whether features of the tumor immune microenvironment could enhance risk stratification, particularly in distinguishing indolent from aggressive disease. We analyzed 116 pT1 colorectal carcinomas, including 94 AJCC Stage I tumors (non-metastatic) and 22 AJCC Stage III/IV tumors (advanced/metastatic). Clinical, histologic, and molecular features, such as tumor grade, vascular invasion, perineural invasion, tumor budding, tumor deposits, and mismatch repair (MMR) status, were assessed. Immune profiling using tissue microarrays and digital image analysis included CD8, FOXP3, CD163, PD-L1, LAG3, HLA-I, HLA-II, and beta-2-microglobulin (B2M). Advanced-stage tumors (Stage III/IV) more frequently showed high-risk histologic features, including lymphovascular invasion (40.9 % vs. 8.6 %, p = 0.007), intramural venous invasion (27.3 % vs. 3.2 %, p = 0.0015), extramural venous invasion (13.6 % vs. 0 %, p = 0.0061), and tumor deposits (mean 0.23 vs. 0.00, p < 0.001). Cribriform morphology was also more common in advanced-stage tumors (38.5 % vs. 8.2 %, p = 0.015). Immune profiling revealed significantly higher densities of CD8⁺ T-cells (503.15 vs. 326.58 cells/mm², p = 0.010), PD-L1⁺ immune cells (90.79 vs. 12.68, p = 0.011), and higher tumor B2M expression (0.21 vs. 0.05, p = 0.020) in AJCC stage I tumors, while the other examined immune biomarkers revealed no significance. While the overall impact of the immune microenvironment remains unclear, this study suggests that combining immune profiling of CD8⁺ T-cell infiltration, PD-L1-positive immune cells, and tumor B2M expression may be useful as an adjunct to conventional histologic assessment to improve prognostic accuracy and guide management of early colorectal cancer.