ArticleCancer medicine2023
LAG-3 transcriptomic expression patterns across malignancies: Implications for precision immunotherapeutics.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 29 citations in OpenAlex.
- Nivolumab and Relatlimab for the Treatment of Patients with Unresectable or Metastatic Mismatch Repair-Proficient Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Transcriptome-Based Synthetic Lethality Predictions to Improve Targeted Therapy/Immunotherapy Treatment Prioritization in Nonmetastatic Breast Cancer: BC-SELECT.Cancer research communications · 2026Article
- Optimizing transcriptome-based synthetic lethality predictions to improve targeted therapy / immunotherapy treatment prioritization in non-metastatic breast cancer: BC-SELECT.bioRxiv : the preprint server for biology · 2026Article
- Checkpoint inhibition and beyond: Precision immune engineering for the immune-privileged landscape of ocular malignancies.BioImpacts : BI · 2026Review
- Modulation of the PD-1/PD-L1 axis and tumor immunity by metals and metalloids: mechanistic insights and human health implications.Frontiers in immunology · 2026Review
- OX40 transcriptomic expression and its association with immune checkpoints and clinical outcomes.Therapeutic advances in medical oncology · 2026Article
- Cracking the resistance code: The molecular reclassification of cancer and precision therapy strategies.Seminars in cancer biology · 2025Review
- CD40 transcriptomic expression patterns across malignancies: implications for clinical trials of CD40 agonists.Cancer immunology, immunotherapy : CII · 2025Article
- Gene- and immune-targeted therapy combinations using dual-matched biomarkers for patient selection.NPJ precision oncology · 2025Article
- Lessons learned from a decade of immune checkpoint inhibition: The good, the bad, and the ugly.Cancer metastasis reviews · 2025Review
- PD-1 transcriptomic landscape across cancers and implications for immune checkpoint blockade outcome.NPJ genomic medicine · 2025Article
- ICOS and ICOS ligand: expression patterns and outcomes in oncology patients.Therapeutic advances in medical oncology · 2025Article
- B7-H3/CD276: Novel Immune Checkpoint and Jack of All Trades.ImmunoTargets and therapy · 2025Review
- Challenges and prospects of LAG-3 inhibition in advanced gastric and gastroesophageal junction cancer: insights from the RELATIVITY-060 trial.Journal of gastrointestinal oncology · 2024Article
- Tumor necrosis factor superfamily signaling: life and death in cancer.Cancer metastasis reviews · 2024Review
- 4-1BB transcriptomic expression patterns across malignancies: Implications for clinical trials of 4-1BB agonists.Cancer communications (London, England) · 2024Article
- OX40/OX40 ligand and its role in precision immune oncology.Cancer metastasis reviews · 2024Review
- Impact of LAG-3/FGL1 pathway on immune evasive contexture and clinical outcomes in advanced urothelial carcinoma.Journal for immunotherapy of cancer · 2024Article
- Clinical and Biologic Correlates of ADORA2A Transcriptomic Expression in Cancer.International journal of molecular sciences · 2024Article
- High indoleamine 2,3-dioxygenase transcript levels predict better outcome after front-line cancer immunotherapy.iScience · 2024Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundLymphocyte activation gene 3 (LAG-3) or CD223 is a transmembrane protein that serves as an immune checkpoint which attenuates T-cell activation. Many clinical trials of LAG-3 inhibitors have had modest effects, but recent data indicate that the LAG-3 antibody relatlimab, together with nivolumab (anti-PD-1), provided greater benefit than nivolumab alone in patients with melanoma.
methodsIn this study, the RNA expression levels of 397 genes were assessed in 514 diverse cancers at a clinical-grade laboratory (OmniSeq: https://www.omniseq.com/). Transcript abundance was normalized to internal housekeeping gene profiles and ranked (0-100 percentile) using a reference population (735 tumors; 35 histologies).
resultsA total of 116 of 514 tumors (22.6%) had high LAG-3 transcript expression (≥75 percentile rank). Cancers with the greatest proportion of high LAG-3 transcripts were neuroendocrine (47% of patients) and uterine (42%); colorectal had among the lowest proportion of high LAG-3 expression (15% of patients) (all p < 0.05 multivariate); 50% of melanomas were high LAG-3 expressors. There was significant independent association between high LAG-3 expression and high expression of other checkpoints, including programmed death-ligand 1 (PD-L1), PD-1, and CTLA-4, as well as high tumor mutational burden (TMB) ≥10 mutations/megabase, a marker for immunotherapy response (all p < 0.05 multivariate). However, within all tumor types, there was inter-patient variability in LAG-3 expression level.
conclusionsProspective studies are therefore needed to determine if high levels of the LAG-3 checkpoint are responsible for resistance to anti-PD-1/PD-L1 or anti-CTLA-4 antibodies. Furthermore, a precision/personalized immunotherapy approach may require interrogating individual tumor immunograms to match patients to the right combination of immunotherapeutic agents for their malignancy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.