Soluble Forms of Pd-1 and Pd-L1 in Blood Plasma of Gastric Cancer Patients and Their Associations With Clinical and Morphological Characteristics of the Disease

Abstract

Results of comparative ELISA investigation of pretreatment sPD-1 and sPD-L1 content in blood plasma of 100 gastric cancer patients at various disease stages aged 25 to 81 years are presented. Control group included 60 practically healthy donors aged 18 - 68 years. Plasma sPD-L1 concentrations did not differ between gastric cancer patients and control group, and sPD-1 levels were statistically significantly lower in patients than in healthy donors (p<0.0001). Positive correlation (R=0.38; p=0.003) was revealed between plasma sPD-1 and sPD-L1 levels in control group and negative (R= -0.26; p=0,009) - in gastric cancer patients. ROC curve revealed the best sPD-1 cut-off level (< 21 pg/ml) with 77% sensitivity and 63.3% specificity, which is not sufficient for its application as diagnostic marker. Statistically significant increase of plasma sPD-L1 from stage I to stage IIIC (R=0.50; p=0.000011) was found. Analysis of associations between the evaluated markers’ levels and indices of gastric cancer expansion according to TNM system revealed statistically significant positive associations of plasma sPD-L1 levels with T (tumor invasion depth) and N (number of affected lymph nodes) indices: R=0.33; p=0.00093, and R=0.27; p=0.0099 respectively. sPD-L1 level was significantly increased in patients with low differentiated adenocarcinoma and cricoid-cell cancer as compared to highly differentiated adenocarcinoma (p=0.02 and p=0.004 respectively); in patients with cricoid-cell cancer it was also higher than in those with moderately differentiated adenocarcinoma (p=0.043) and undifferentiated cancer (p=0.049). Plasma sPD-1 level did not depend on disease stage, TNM system indices and tumor histological structure. Thus, soluble ligand sPD-L1, but not its receptor sPD-1, plasma level is increased in patients with unfavorable clinical and morphological characteristics, may be regarded as potentially valuable prognostic factor for gastric cancer patients’ survival, and probably as a predictor of anti - PD-1/PD-L1 treatment efficiency.

Unbalanced expression of sICOS and sPD‐1 correlates with tumor progression in gastric cancer

“…Gershtein et al reported similar results regarding sPD-1 lower levels in GC, 27 while sICOS previous studies in GC are sparse. We did not find a significant association between sICOS and sPD-1 expression and Lauren histologic type or the WHO grade of differentiation.…”

“…These findings suggest that there is a lower production of sICOS and sPD‐1 by activated lymphocytes in GC, reflecting a T cell activation dysregulated environment as a response to gastric tumor cells. Gershtein et al reported similar results regarding sPD‐1 lower levels in GC, 27 while sICOS previous studies in GC are sparse. We did not find a significant association between sICOS and sPD‐1 expression and Lauren histologic type or the WHO grade of differentiation.…”

How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches

“…Recent evidence has shown that patients with GC have higher serum soluble PD-L1 (sPD-L1) concentrations than healthy controls. Moreover, both elevated tissue PD-L1 and serum sPD-L1 were independent prognostic factors for poor OS and poor DFS in GC patients who underwent surgery [70][71][72]. Lymphocyte activation gene 3 (LAG3) is a checkpoint receptor localized on activated T cell surfaces and NK cells.…”