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.

• Authors: Qiong-Yuan Chen, Wen-Jun Zhou, Jiang-Gang Zhang, Xia Zhang, Qiu-Yue Han, Aifen Lin, Wei-Hua Yan
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 109 Pg. 108798 (Aug 2022) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 35569305 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• HLA-G Antigens
• LILRB2 protein, human
• Membrane Glycoproteins
• Receptors, Immunologic

Topics

• Cell Count
• Female
• Flow Cytometry
• HLA-G Antigens (genetics)
• Humans
• Membrane Glycoproteins (immunology)
• Prognosis
• Receptors, Immunologic (immunology)
• Stomach Neoplasms (pathology)