Clinical Significance of PD-L1, LAG3, and VISTA in Patients With Poorly Cohesive Cell Gastric Cancer

Background/Aim: Compared to other histological gastric cancer subtypes, poorly cohesive cells gastric cancer (PCC-GC) is characterized by a distinct set of epidemiological, histological, and clinical features requiring a specific diagnostic and therapeutic approach. This study analyzed the expression of programmed cell death protein ligand-1 (PD-L1), lymphocyte-activation gene 3 (LAG3), and V-domain suppressor of T cell activation (VISTA) and their impact on the survival of patients with PCC-GC.

Patients and Methods: We retrospectively collected 230 surgically resected stage II/III PCC-GC cases. After LAG3, VISTA, and PD-L1 immunostaining, VISTA expression was assessed in immune (ICs) and tumor cells (TCs). The clinicopathological and prognostic significance of these biomarkers were evaluated.

Results: The median patient’s age was 60 years (range=31-86 years). Additionally, 126 patients (54.8%) were males, and 104 patients (45.2%) were females. Ninety-eight patients (42.6%) had stage II PCC-GC, and 132 patients (57.4%) had stage III PCC-GC. LAG3 over-expression was observed in 9.6% of PCC-GC cases. VISTA in ICs and PD-L1 were over-expressed in 73.0% and 13.9% of the cohort, respectively. Expression of VISTA in ICs was more frequently observed in stage III PCC-GC (p= 0.02). LAG3 and VISTA positivity in ICs served as favorable outcome indicators for disease-free survival, although without statistically significant difference (p=0.054). PD-L1 expression did not have a prognostic value in patients with PCC-GC.

Conclusion: VISTA-IC positivity was significantly associated with the pathologic stage. Since a higher LAG3 and VISTA-IC expression showed a tendency to predict favorable patient outcomes, these immune-related markers might serve as prognostic and therapeutic indicators for patients with PCC-GC.