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Life sciences · Journal article
Frontiers in Genetics · October 22, 2026
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Background Immune checkpoint inhibitors (ICIs) have changed advanced gastric cancer (GC) treatment, but response remains heterogeneous. Radical gastrectomy causes transient perioperative immune perturbations. We evaluated whether early enteral nutrition (EEN) was associated with preservation of peripheral immune-cell phenotypes and improved postoperative outcomes. Immunotherapy-related interpretations were exploratory; no ICI therapy or molecular pathway assays were performed. Methods This retrospective cohort included 120 patients undergoing radical gastrectomy (January 2022-December 2023): EEN within 24 h (n = 60) or traditional delayed nutrition (TN) on postoperative day (POD) 3–5 (n = 60). The primary endpoint was the POD 7 CD4 + /CD8 + ratio. Exploratory secondary endpoints included immune-cell counts, 30-day complications, nutritional and gastrointestinal recovery, hospital utilization, and quality-of-life measures. Driver mutations described baseline context only; no mutation-stratified outcome analyses were performed. Results On POD 7, the CD4 + /CD8 + ratio was higher with EEN than TN (1.42 ± 0.18 vs. 1.26 ± 0.21; mean difference, 0.16; 95% CI, 0.09-0.23; P < 0.001). CD4 + (512 ± 68 vs. 456 ± 72 cells/μL), CD3 + (1,235 ± 152 vs. 1,086 ± 168 cells/μL), and NK-cell counts (285 ± 42 vs. 248 ± 38 cells/μL) were also higher (all P < 0.001), whereas CD8 + counts did not differ (P = 0.743). Overall postoperative complications were lower with EEN (15.0% vs. 31.7%; risk ratio, 0.47; 95% CI, 0.23-0.96; P = 0.031), and postoperative hospital stay was shorter (10.3 ± 2.1 vs. 13.8 ± 2.9 days; P < 0.001). Secondary comparisons were exploratory and unadjusted for multiplicity. Conclusion Perioperative EEN was associated with better preservation of selected peripheral immune-cell phenotypes, fewer postoperative complications, and faster recovery after gastrectomy for GC. CD4 + /CD8 + ratio and NK-cell counts are phenotypic markers, not direct measures of IFNG / IL2 or NFKB1 / IL6 pathway activity. Immunotherapy implications remain hypothesis-generating and require prospective validation.