ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2026
Hampered CD8 + ILT2 + T cell activation by HLA-G suggests a new immune checkpoint in gastric adenocarcinoma.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Identification of a novel ion channel-related gene signature to predict prognosis and immune response of gastric cancer.Translational cancer research · 2026Article
- Prognostic impact of HLA-G expression in cervical squamous cell carcinoma: correlation with PD-L1 and CD8-positive tumor infiltrating lymphocytes.Frontiers in immunology · 2026Article
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Abstract
backgroundImmune checkpoint inhibitors (ICI) are pivotal in cancer treatment. However, not all patients are responsive to current ICI therapies, and new targets are needed. Thus, the HLA-G/ILT2 pathway emerges as one such potential ICI. The present study aimed to analyze the implications of this pathway in cytotoxic T cells from patients with gastric adenocarcinoma.
methodsPeripheral blood mononuclear cells (PBMCs), and tissue infiltrating lymphocytes were obtained from 16 patients with gastric adenocarcinoma. PBMCs from 17 healthy subjects were used as controls. Cells were subjected to flow cytometry on the one hand and stimulation (assessed by IFNγ production) and proliferation assays, in the presence or absence of HLA-G, on the other.
resultsDespite lower CD3 + counts (p = 0.0036), CD3 + CD8 + ILT2 + (ILT2 + Tc) cells are overrepresented in patients, compared to control subjects (p < 0.0001). These ILT2 + Tc exhibit enhanced anti T-cell receptor (TCR)-stimulated IFNγ production, compared to its counterparts ILT2- Tc (p = 0.0039), which was impaired by the presence of HLA-G (p = 0.0002). Proliferative responses of Tc were significantly reduced by HLA-G (p < 0.0001) after 5 days of stimulation. Finally, simultaneously PD1 and ILT2 staining revealed differential expression patterns between patients.
conclusionsCD8 + T cells expressing ILT2 are overrepresented in patients with gastric adenocarcinoma, independent of PD-1 expression, and appear particularly susceptible to functional suppression in the presence of HLA-G-positive tumors. These findings highlight the immunomodulatory role of HLA-G in the tumor microenvironment and support its relevance as a potential target for personalized immunotherapeutic strategies.
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