ArticleCommunications medicine2023
Development and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit.
Article in Communications medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03061305 (An Observational Trial Assessing the Clinical Benefit of Molecular Profiling in Patients With Solid Tumors), which is not on this map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
An Observational Trial Assessing the Clinical Benefit of Molecular Profiling in Patients With Solid Tumors
Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Trial
- TAMs in the Gynecological Tumor Microenvironment: Insights from Cross-Cancer Studies for Immunotherapy.Cancers · 2026Review
- Immunotherapy for pediatric solid tumors: overcoming biological barriers through rational multimodal combinations.Cancer immunology, immunotherapy : CII · 2026Review
- Biomarkers and ImmuneScores in lung cancer: predictive insights for immunotherapy and combination treatment strategies.Biological procedures online · 2025Review
- PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities.Clinical and experimental medicine · 2025Review
- Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate.The oncologist · 2025Article
- Tumour Mutational Burden and Immune Checkpoint Inhibitor Response in Non-small Cell Lung Cancer: A Continuous Modelling Approach.Targeted oncology · 2025Article
- Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway.Cell death discovery · 2025Article
- Predictive value of ENLIGHT-DP in patients with metastatic lung adenocarcinoma treated with immune checkpoint inhibitors and platinum chemotherapy directly from histopathology slides using inferred transcriptomics.Journal for immunotherapy of cancer · 2025Article
- The Impact of Pembrolizumab as a Salvage Therapy Based on HER2 Expression in Advanced Gastric Cancer.Cancers · 2024Article
- Article
- Construction and validation of a gene expression classifier to predict immunotherapy response in primary triple-negative breast cancer.Communications medicine · 2023Article
- Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit.Cancer research communications · 2023Article
- LRP1B mutation is associated with tumor immune microenvironment and progression-free survival in lung adenocarcinoma treated with immune checkpoint inhibitors.Translational lung cancer research · 2023Article
- Tumour-associated macrophages: versatile players in the tumour microenvironment.Frontiers in cell and developmental biology · 2023Review
- Incorporating lesion-to-lesion heterogeneity into early oncology decision making.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
42 authors at 20 institutions in 2 countries.
Funding
Abstract
backgroundAnti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction.
methodsUsing treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients.
resultsHere, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 patients; 26 tumor types; IRS-High or -Low groups). In the 248 patient validation cohort (248 patients; 24 tumor types; non-pembrolizumab PD-[L]1 monotherapy treatment), median rwPFS and OS are significantly longer in IRS-High vs. IRS-Low patients (rwPFS adjusted hazard ratio [aHR] 0.52, p = 0.003; OS aHR 0.49, p = 0.005); TMB alone does not significantly predict PD-(L)1 rwPFS nor OS. In 146 patients treated with systemic therapy prior to pembrolizumab monotherapy, pembrolizumab rwPFS is only significantly longer than immediately preceding therapy rwPFS in IRS-High patients (interaction test p = 0.001). In propensity matched lung cancer patients treated with first-line pembrolizumab monotherapy or pembrolizumab+chemotherapy, monotherapy rwPFS is significantly shorter in IRS-Low patients, but is not significantly different in IRS-High patients. Across 24,463 molecularly-evaluable trial patients, 7.6% of patients outside of monotherapy PD-(L)1 approved tumor types are IRS-High/TMB-Low.
conclusionsThe validated, predictive, pan-tumor IRS model can expand PD-(L)1 monotherapy benefit outside currently approved indications.
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Registered trials
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.