Analysis of Immune Cell Infiltration Distribution and Prognostic Value in Obstructive Colorectal Cancer

Objective: This study aims to determine how intestinal obstruction influences the tumor immune microenvironment (TIME) and its impact on prognosis in colorectal cancer (CRC). Methods: Immune cell densities (CD4⁺, CD8⁺, CD20⁺, CD68⁺) within central tumor (CT) and invasive margin (IM) compartments were quantitatively analyzed using immunohistochemistry (IHC) and QuPath digital pathology in surgical resection samples from 328 patients (164 obstructed colon cancer [OCRC] vs. 164 non-obstructed [NOCRC], cohorts matched by propensity scoring). Findings on tumor-infiltrating immune cell spatial distribution were integrated with peripheral blood immune cell counts and clinicopathological characteristics to characterize the obstructed colon cancer immune microenvironment. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated. Results: OCRC exhibited higher lymphocytic infiltration, particularly in the CT compartment, compared to NOCRC, with significantly elevated CT-CD8⁺ T cell density in T4-stage OCRC (p < 0.005). Obstruction enhanced immune cell correlations across compartments, especially in T4 tumors, and the CD68⁺/CD8⁺ ratio effectively discriminated obstruction status (CT area under the curve (AUC): T4 = 0.879). Peripheral lymphocytopenia was pronounced in obstructive cases (p = 0.003). Critically, T4 OCRC showed a complete loss of all correlations between tumor-infiltrating immune cells and peripheral parameters. Despite increased infiltration, high CD8⁺ density in OCRC correlated with worse prognosis, indicating a paradoxical role influenced by obstruction context. CD68⁺ macrophages in the invasive margin consistently predicted improved survival (Disease-free survival [DFS]: Hazard ratio [HR] = 0.59, p = 0.008). Conclusions: Intestinal obstruction in CRC, particularly in T4-stage tumors, may represent an immunologically active state that alters local immune infiltration and systemic-local immune crosstalk. These findings suggest that obstruction status could refine prognostic stratification and inform therapeutic strategies, although validation in larger cohorts is warranted.