Prognostic significance of the immune checkpoint HLA-G/ILT-4 in the survival of patients with gastric cancer

Abstract

Objective: Human leukocyte antigen-G (HLA-G) and its receptors, including immunoglobulin-like transcripts (ILT)-2 and ILT-4, are closely associated with cancer development and clinical outcomes of patients. However, the clinical significance of HLA-G and ILT-2/-4 in gastric cancer (GC) is limited.

Methods: In this study, the percentage of HLA-G-, ILT-2 and ILT-4 positive tumor cells in 127 GC lesion suspensions of tumor cells gated for epithelialcelladhesionmolecule(EpCAM) was determined using multicolor flow cytometry and their clinical significance was evaluated.

Results: Our data showed that the median percentages of HLA-G-, ILT-2, and ILT-4 expressing GC cells were 18.0%, 67.80%, and 1.42%, respectively, and co-expression of HLA-G/ILT-2, HLA-G/ILT-4, and ILT-2/ILT-4 was 16.9%, 1.42%, and 1.70%, respectively. Kaplan-Meier survival results revealed that besides post-operation N status (p = 0.006), M status (p = 0.001), and AJCC clinical stage (p < 0.001), only high percentage of ILT-4⁺ GC cells was a significant factor for worse survival of patients with GC (overall survival [OS]: 42.9 months vs. 84.5 months; p = 0.031). However, among female patients with GC (n = 31), high percentage of either HLA-G⁺ (OS: 18.5 months vs. 89.3 months; p = 0.001) or ILT-4⁺ (OS: 17.9 months vs. 85.8 months; p = 0.002) GC cells was markedly associated with a poor prognosis.

Conclusion: Our findings revealed that among HLA-G, ILT-2, and ILT-4, only a high percentage of ILT-4⁺ GC cells was significantly related to poor prognosis in the entire cohort of patients with GC. However, high percentage of HLA-G⁺ and ILT-4⁺ GC cells is associated with poor clinical outcome among female patients with GC.

Keywords: Gastric cancer; HLA-G; ILT-2; ILT-4; Immune checkpoint; Prognosis.