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

TL;DR

This study shows that intestinal obstruction in colorectal cancer changes the tumor's immune environment and affects patient outcomes, especially in advanced stages.

Contribution

The study reveals how obstruction alters immune cell infiltration and its paradoxical impact on prognosis in T4-stage colorectal cancer.

Findings

Obstructed tumors showed higher lymphocytic infiltration, especially CD8+ T cells in the central tumor compartment.

T4 obstructive tumors had a complete loss of correlation between tumor and peripheral immune parameters.

CD68+ macrophages in the invasive margin predicted better survival in obstructed colorectal cancer.

Abstract

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.

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