Published online Oct 28, 2026. doi: 10.3748/wjg.120447
Revised: March 31, 2026
Accepted: April 21, 2026
Published online: October 28, 2026
Processing time: 197 Days and 6.3 Hours
Gastric cancer is a major global health challenge, with sintilimab plus chemo
To investigate the relationship between peripheral blood cytokines and long-term prognosis in AGC patients treated with sintilimab combined with chemotherapy.
Clinical and pathological information, along with pretreatment peripheral blood cytokine levels, were collected from 101 patients who received sintilimab in conjunction with chemotherapy at the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) between January 2021 and January 2023. To determine optimal cutoff values for baseline cytokines, receiver operating characteristic (ROC) curves were generated using cytokine levels measured prior to immunotherapy, subsequently classifying patients into high and low cytokine level groups. The correlations between cytokines and clinicopathological factors were assessed using both the χ2 test and t-test. To evaluate the dynamic predictive value of continuous cytokine levels at 9-, 12-, and 18-month, time-dependent ROC curves were utilized. The Kaplan-Meier method and log-rank tests facilitated the comparison of survival curves. Variables showing P < 0.05 in univariate Cox regression analysis were chosen for the least absolute shrinkage and selection operator-Cox multivariate regression analysis to pinpoint independent prognostic factors for progression-free survival (PFS) and overall survival (OS). A nomogram for predicting OS was constructed using the entire cohort and was internally validated through 1000 bootstrap resamples. To evaluate the robustness of the model, ROC curves, calibration curves, and concordance indices (C-indices) were calculated at 9-, 12-, and 18-month. The primary endpoints of the study were OS and PFS. All statistical tests were two-tailed, considering significance at α = 0.05 (P < 0.05).
Optimal cytokine cutoff values were determined using ROC curves: Interleukin (IL)-4 0.34 pg/mL, IL-6 2.12 pg/mL, IL-8 9.09 pg/mL, IL-10 4.10 pg/mL, and IL-17 3.03 pg/mL. Groups with low IL-6, IL-10, and IL-17 had significantly better PFS and OS (P < 0.05), while IL-4 and IL-8 had no impact. After adjusting for the specific chemotherapy backbone using Firth’s penalized Cox regression, high levels of IL-10 and IL-17 remained highly significant independent risk predictors for both PFS and OS, while IL-6 was an independent predictor exclusively for PFS. Furthermore, programmed death-ligand 1 (PD-L1) positivity and positive Epstein-Barr virus status were also identified as significant independent prognostic factors for OS.
PD-L1 expression and peripheral blood cytokine levels of IL-10 and IL-17 are independent prognostic factors for OS, while IL-6 is an independent prognostic factor exclusively for PFS in AGC patients treated with sintilimab combined with chemotherapy, potentially serving as biomarkers to identify patients who benefit from immunotherapy.
Core Tip: This study explores advanced gastric cancer (AGC) patients receiving first-line sintilimab plus chemotherapy, identifying baseline interleukin (IL)-6, IL-10, IL-17 and programmed death-ligand 1 as independent overall survival prognostic factors. A well-validated nomogram model is established, and these peripheral blood indices serve as novel biomarkers for screening AGC patients who benefit from immunotherapy.