ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
Combined inhibition of PD-1/PD-L1, Lag-3, and Tim-3 axes augments antitumor immunity in gastric cancer-T cell coculture models.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Cellular Senescence and Immunosenescence in Melanoma: Insights From the Tumor Microenvironment.Cancer medicine · 2025Pooled it
- Association of PD-L1 Expression with Clinicopathologic Characters in Gastric Cancer: A Comprehensive Meta-analysis.Current medicinal chemistry · 2024Pooled it
- Fgl-1 promotes the progression of endometrial adenocarcinoma through PI3K/AKT signal pathway.Medical oncology (Northwood, London, England) · 2026Article
- HBsAg-tagged tumour vaccine system eliminates solid tumours through virus-specific memory T cells.Nature biomedical engineering · 2026Article
- Clinicopathological features and immune checkpoint expression patterns in dMMR early gastric cancer: a retrospective pilot study.BMC cancer · 2026Article
- Perineural invasion in digestive tract tumors: Immune system interactions and therapeutic strategies.World journal of clinical oncology · 2026Review
- Targeting T cell exhaustion in colorectal cancer: emerging roles of LAG-3, TIM-3, and TIGIT signaling in overcoming immunotherapy resistance.Cell communication and signaling : CCS · 2026Review
- Development of combinatorial immunotherapy for patients with advanced gastric cancer from the perspective of immunosuppressive mechanisms in the tumor microenvironment.Fukushima journal of medical science · 2026Review
- Proteogenomic profiling of soft tissue leiomyosarcoma reveals distinct molecular subtypes with divergent outcomes and therapeutic vulnerabilities.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- Dynamic tumor-infiltrating lymphocytes predicts survival in HR+/HER2- early breast cancer: a pre-to-post neoadjuvant chemotherapy study.Breast cancer research : BCR · 2025Article
- Article
- Advancing Cancer Treatment: A Review of Immune Checkpoint Inhibitors and Combination Strategies.Cancers · 2025Review
- Applications and challenges of immunotherapy in the management of gastric adenocarcinoma: current status and future perspectives.World journal of surgical oncology · 2025Review
- Targeting archetypes of viral-driven cancers with immunotherapy: a perspective on immunogenicity within the tumor microenvironment.Frontiers in immunology · 2025Review
- Dual checkpoint blockade of PD-1 and Tim-3 by engineered hybrid nanovesicles for enhanced cancer immunotherapy.Frontiers in immunology · 2025Article
- Therapeutic opportunities in EBV-positive gastric cancer subtypes.Therapeutic advances in medical oncology · 2025Review
- Mechanisms, advances, and challenges of immunotherapy in gastric cancer.Frontiers in immunology · 2025Review
- Immune checkpoints in immune response to glioma: two sides of the same coin.Frontiers in immunology · 2025Review
- Research advances in the molecular classification of gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Review
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundImmunotherapy targeting PD-1 provides a limited survival benefit in patients with unresectable advanced or recurrent gastric cancer (GC). Beside PD-L1, the expression of inhibitory ligands such as CEACAM-1 and LSECtin on GC cells account for this limitation. Here we assessed their expression and immune suppressive effect in GC patients.
methodsUsing multiplexed immunohistochemistry staining, we evaluated the distribution of different inhibitory ligands, including PD-L1, CEACAM-1, LSECtin, and MHC class II, in 365 GC patients. We analyzed their correlations and overall survival (OS) based on the expression of each inhibitory ligand and the independent prognostic factors that affect OS. Subsequently, we evaluated the additive effect of anti-PD-1 mAb or anti-PD-L1 mAb with/without anti-Lag-3 mAb with/without anti-Tim-3 mAb in cytotoxic assay using tumor-antigen specific CTL clones against GC cell lines.
resultsCo-expression of the inhibitory ligands for PD-1, Tim-3, and Lag-3 was observed in the largest proportion (34.7%). CEACAM-1, LSECtin, and MHC class II expression showed significant correlation with PD-L1 expression and OS. Multivariable analysis demonstrated that CEACAM-1 low is an independent prognostic factor. Furthermore, combining dual and triple ICIs yielded additive effect on cytotoxicity of CTL clones against each immune inhibitory ligand positive GC cell lines.
conclusionsOur findings suggested that the expression of inhibitory ligands for Tim-3 and Lag-3 on GC cells serve as potential biomarkers to predict the response to anti-PD-1 therapy and the combinatorial immunotherapy with ICIs targeting for PD-1, Tim-3, and Lag-3 has a therapeutic potential for GC patients.
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