To explore the predictive value of soluble immune checkpoints for the efficacy and prognosis of immunotherapy in patients with gastric cancer.

From April 2021 to July 2022, clinical data of patients with gastric cancer who received first-line SOX chemotherapy combined with PD-1 inhibitor at the Cancer Center of Changzhou No.2 People′s Hospital Affiliated to Nanjing Medical University were collected.Concentrations of sIL-2Ra(CD25), s4-1BB, sCD86, sCTLA-4, Free Active TGF-β1, sPD-1, sPD-L1, sTIM-3, sLAG-3, sGalectin-9 were detected before treatment and at the time of disease progression.Mann-Whitney U test was used to compare the differences of soluble immune checkpoints concentration before treatment between patients with partial response(PR)and those without PR [disease stability(SD)+ disease progression(PD)]. Logistic regression analysis was used to explore independent factors of efficacy prediction.Kaplan-Meier and COX regression analysis were used to explore soluble immune checkpoints affecting prognosis, and Wilcoxon signed-rank test was used to compare the changes of soluble immune checkpoints before and after treatment.

A total of 40 patients with gastric cancer were incorporated into the analysis, with 17(42.5%)patients evaluated as PR, 17(42.5%)as SD, and 6(15.0%)as PD.Before treatment, the concentrations of sPD-1, sPD-L1, and sGalectin-9 in the PR group were significantly higher than those in the SD+ PD group(6.27 pg/ml vs.3.49 pg/ml, P=0.0043; 7.96 pg/ml vs.7.31 pg/ml, P=0.0014; 15 083.09 pg/ml vs.8533.77 pg/ml, P=0.0024). Patients with high serum sPD-1 concentration before treatment(sPD-1>4.21 pg/ml)showed significantly longer progression free survival(P<0.001, HR=0.18, 95% CI: 0.08-0.41, P<0.0001). sPD-1 was an independent predictor of best overall response(BOR)in the treatment of gastric cancer patients.Seventeen patients showed a significant increase in sCD86 at the time of disease progression compared to baseline(74.62 pg/ml vs.49.71 pg/ml, P=0.0038).

sPD-1 can act as a predictive factor for BOR of immunotherapy in gastric cancer patients, and the increase in sCD86 after immunotherapy may be the reason for immunotherapy resistance.