Expression Patterns of Immune Checkpoint Molecules and Their Clinical Values in Gastric Neuroendocrine Neoplasms.

Introduction: Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach tumor. However, limited data exist about the expression and clinical significance of B7 family ligands/receptors in patients with g-NENs. Thus, we conducted this study to address this issue in a cohort of 112 patients with g-NENs.

Methods: Using immunohistochemistry, we mapped and quantified the expression of the B7 family ligands/receptors in 112 g-NEN samples: programmed cell death ligand 1 and 2 (PD-L1 and PD-L2), B7-H3, B7-H4, recombinant human galectin-9 (LGALS9), and CD155. Associations between the marker levels, clinicopathological variables, and survival were evaluated.

Results: The percentages of high expression of PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 in the cohort of 112 g-NEN cases were 37.5%, 55.4%, 46.4%, 37.5%, 46.4%, and 51.8%, respectively. Elevated expression of PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 was significantly associated with several clinicopathological characteristics. K-M analysis indicated that high expression levels of CD155, B7-H3, PD-L2, and LGALS9 were correlated with poor overall survival (OS) ( P < 0.0001, P = 0.0002, P = 0.0319 and P = 0.0120, respectively). Multivariate Cox regression analysis indicated that high CD155 expression, vasculature invasion, and worse World Health Organization pathological grade were independent prognostic factors for OS ( P = 0.007, P = 0.030, and P = 0.019, respectively).

Discussion: We detected variable expression of the PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 proteins in g-NENs. These results suggest that the expression level of CD155 may be a vital indicator of OS in patients with g-NENs. B7 family ligands/receptors could be potential immunotherapeutic targets for g-NENs.