ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2020
Immune suppression caused by PD-L2 expression on tumor cells in gastric cancer.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Prognostic Impact of Immunoscore in Pathological Stage III Differentiated Gastric Cancer: A Multicenter Cohort Study Including PD-L1/PD-L2 Expression Analysis.Annals of gastroenterological surgery · 2026Article
- Integrated Weighted Gene Co-Expression Network and Single-Cell RNA Sequencing Analyses Reveal the Prognostic Significance of Hypoxia in Gastric Cancer.Biomedicines · 2026Article
- The expression and prognostic predictive value of PD-L2 in patients undergoing radical gastric cancer surgery.Future science OA · 2025Article
- Anti-PD-L2 immunotherapy is efficacious against melanoma in aged hosts through IL-17 and IFNγ signalling.Nature communications · 2025Article
- ALAD as a prognostic biomarker regulates metabolism and immune responses in renal cell carcinoma through multi-omics analysis.Translational oncology · 2025Article
- PD-1, PD-L1, and PD-L2 Expression as Predictive Markers in Rare Feline Mammary Tumors.Veterinary sciences · 2025Article
- CYP19A1 Silencing Inhibits Cell Proliferation and Endoplasmic Reticulum Stress in Stomach Adenocarcinoma.Oncology research · 2025Article
- The influence ofFrontiers in immunology · 2025Article
- PD-L2 of tumor-derived exosomes mediates the immune escape of cancer cells via the impaired T cell function.Cell death & disease · 2024Article
- Aberrant DNA polymerase beta expression is associated with dysregulated tumor immune microenvironment and its prognostic value in gastric cancer.Clinical and experimental medicine · 2024Article
- SPHK1 promotes bladder cancer metastasis via PD-L2/c-Src/FAK signaling cascade.Cell death & disease · 2024Article
- Biomarker-oriented chemo-immunotherapy for advanced gastric cancer.International journal of clinical oncology · 2024Review
- Comparison of Clinical Trial Results of the Recently Approved Immunotherapeutic Drugs for Advanced Biliary Tract Cancers.Reviews on recent clinical trials · 2024Review
- Programmed cell death-ligand 2: new insights in cancer.Frontiers in immunology · 2024Review
- PD-L2 Expression in Breast Cancer Promotes Tumor Development and Progression.Journal of immunology research · 2024Article
- Identification of lncRNA dual targeting PD-L1 and PD-L2 as a novel prognostic predictor for gastric cancer.Frontiers in oncology · 2024Article
- Immunology and immunotherapy in gastric cancer.Clinical and experimental medicine · 2023Review
- Integrated single-cell RNA sequencing analysis reveals a mesenchymal stem cell-associated signature for estimating prognosis and drug sensitivity in gastric cancer.Journal of cancer research and clinical oncology · 2023Article
- Nivolumab versus irinotecan as third- or later-line treatment for advanced gastric cancer: a multi-center retrospective study.International journal of clinical oncology · 2023Article
- Evolving landscape of PD-L2: bring new light to checkpoint immunotherapy.British journal of cancer · 2023Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundGastric cancer (GC) patients with PD-L1-negative tumor occasionally have a favorable response to anti-PD-1 mAb. The aim of the present study was to investigate the regulatory mechanism and immunosuppressive role of PD-L2 in GC.
methodsWe used immunohistochemistry to evaluate the expression of PD-L2 in primary tumors from 194 patients with GC. The mechanism of PD-L2 expression was assessed in TCGA stomach adenocarcinoma tissue dataset and in vitro assay using GC cell lines. The immunosuppressive role of PD-L2 was evaluated by cytotoxicity of CTL clone against PD-L2 expressing GC cells.
resultsPD-L2 was expressed on tumor cells (TCs) of 28.4% patients and PD-L2 expression on TCs was significantly associated with tumor progression. TCGA dataset revealed that IFN-γ and, to a lesser extent, IL-4 signature significantly correlated with PD-L2 expression. In vitro assay showed that IFN-γ and, also to a lesser extent, IL-4 can upregulate PD-L2 expression on GC cells. Anti-PD-L2 mAb significantly enhanced the cytotoxicity of CTL clone against GC cell lines expressing PD-L2.
conclusionsPD-L2 is expressed on GC cells and PD-1/PD-L2 interaction are functionally involved in anti-tumor CTL activities. PD-L2 expression should be considered when determining the optimal immunotherapy for GC.
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