Published online Feb 27, 2026. doi: 10.4240/wjgs.v18.i2.113530
Revised: November 4, 2025
Accepted: December 11, 2025
Published online: February 27, 2026
Processing time: 155 Days and 23.2 Hours
Gastric cancer remains a major global health burden with high mortality due to late-stage diagnosis and limited treatment efficacy. Emerging evidence demon
To investigate the spatial distribution pattern, density, and proportional features of important immune cells in the tumor microenvironment following radical gastrectomy for gastric cancer, assess their relationships with patients’ 5-year overall survival (OS) and recurrence-free survival following surgery, and provide an immunological foundation for prognostic assessment.
A total of 112 patients with stage I-III gastric cancer who underwent R0 resection between June 2018 and June 2020 were included retrospectively. Paraffin-embedded specimens of postoperative cancer tissues and adjacent tissues were collected. The multicolor immunohistochemistry technique was used, and pan-cytokeratin staining was performed synchronously with 4,6-diamidino-2-phenylindole nuclear staining. The sections were scanned by the Vectra Polaris™ full-spectrum imaging system, and cell phenotype identification and spatial localization analysis were performed via InForm® 2.6 software. The independent prognostic value of OS/disease-free survival and immunological markers was assessed (tumor-node-metastasis stage, Lauren classification), and the Kaplan-Meier survival curve was used to analyze the survival differences between the high/low immune infiltration groups (log-rank test).
The density of CD8+ T cells in the invasion margin area (median: 248.5/mm2) was significantly greater than that in the tumor core area (108.3/mm2, P < 0.001). The 5-year OS rate was high in patients with a high CD8+ density (> 220/mm2; 68.2%), low-density group: 42.1%, P = 0.003. An independent correlation between extended disease-free survival and a CD8+/forkhead box protein 3+ (FoxP3+) ratio > 2.5 was found [hazard ratio (HR) = 0.47, 95% confidence interval (CI): 0.29-0.76]. The risk of death was greater for those with a fraction of programmed death ligand 1+ tumor cells > 10% (HR = 2.15, 95%CI: 1.32-3.51). The enrichment of CD68+CD163+ M2 macrophages in the core area of the tumor predicted an increased risk of recurrence (HR = 1.72, P = 0.018). An immune prognosis scoring system was constructed on the basis of least absolute shrinkage and selection operator (regression, integrating the density of the CD8+ marginal zone, the CD8+/FoxP3+ ratio, and the 5-year OS prediction area under the curve was 0.81 (95%CI: 0.74-0.88).
The spatial distribution pattern of immune cells in the tumor microenvironment following gastric cancer surgery and the percentages of particular subgroups (programmed death ligand 1+ and CD8+/FoxP3+ tumor cells) are independent predictors of long-term survival.
Core Tip: This retrospective cohort study evaluated spatial distribution patterns of immune cells in the tumor microenvironment after radical gastrectomy for gastric cancer using multiplex immunohistochemistry. High CD8+ T-cell density at the invasive margin, a CD8+/forkhead box protein 3+ ratio > 2.5, and low programmed death ligand 1+ tumor cell proportion were independent predictors of favorable survival. An immune prognostic score integrating these features achieved high accuracy in predicting 5-year overall survival. These findings highlight the prognostic value of immune cell spatial profiling and may guide individualized postoperative immunotherapy strategies.