# Prognostic Impact of Immunoscore in Pathological Stage III Differentiated Gastric Cancer: A Multicenter Cohort Study Including PD‐L1/PD‐L2 Expression Analysis

## TL;DR

The study shows that Immunoscore can predict better survival in a specific type of advanced gastric cancer, suggesting it could guide treatment decisions.

## Contribution

The study demonstrates that Immunoscore is an independent prognostic factor specifically in differentiated-type stage III gastric cancer.

## Key findings

- In differentiated-type GC, high Immunoscore correlates with better recurrence-free and overall survival.
- Immunoscore is an independent prognostic factor for survival in differentiated-type GC but not in undifferentiated-type GC.
- PD-L1/2 expression was not a prognostic factor in the overall cohort.

## Abstract

The clinical use of the tumor microenvironment as a biomarker remains difficult in gastric cancer (GC). This multicenter, retrospective cohort study assessed the prognostic ability of the Immunoscore (IS) and the expression of programmed death ligand 1 (PD‐L1) or programmed death ligand 2 (PD‐L2) to select GC patients at higher risk of recurrence who may therefore require more intensive perioperative treatment.

In 184 untreated pStage III GC patients who underwent radical gastrectomy at 13 institutions, IS (CD3+ and CD8+ lymphocytes) and PD‐L1/2 expression were analyzed by immunohistochemistry using digital pathology HALO software. The associations between clinicopathological factors and prognosis were assessed.

Neither IS nor PD‐L1/2 expression was a prognostic factor in the overall cohort. Subgroup analysis by histological type showed that in patients with differentiated‐type GC, the high IS group had significantly better recurrence‐free survival (RFS) (hazard ratio, 0.39; 95% confidence interval, 0.19–0.78; log‐rank p = 0.006) and overall survival (OS) (hazard ratio, 0.39; 95% confidence interval, 0.19–0.82; log‐rank p = 0.009) than the low IS group, whereas in undifferentiated‐type cases, IS was not associated with RFS or OS. Cox multivariate analysis revealed that IS was an independent prognostic factor for RFS (p = 0.024) and OS (p = 0.017) only in differentiated‐type cases.

Histological classification may be useful in assessing the tumor microenvironment in GC, and patients with differentiated‐type pStage III with a low IS signature may be candidates for more intensive perioperative treatment due to their higher risk of recurrence.

We assessed the prognostic ability of the Immunoscore and PD‐L1 or PD‐L2 expression in pStage III GC patients by immunohistochemistry. The results showed that Immunoscore was an independent prognostic factor in differentiated GC, but not in undifferentiated GC.