ArticleCancer immunology, immunotherapy : CII2024
CD74 is associated with inflamed tumor immune microenvironment and predicts responsiveness to PD-1/CTLA-4 bispecific antibody in patients with solid tumors.
Article in Cancer immunology, immunotherapy : CII, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03261011 (A Phase 1A/1B Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK104 in Subjects With Advanced Solid Tumors), which is not on this map. Cited by 12 papers.
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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.
A Phase 1A/1B Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK104 in Subjects With Advanced Solid Tumors
Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- CD74Journal of gastrointestinal cancer · 2026Article
- Review
- BET Protein Degrader ZBC260 Induces Tumor Vascular Reprogramming Through Endothelial Cell Remodeling.Breast cancer (Dove Medical Press) · 2026Article
- Disordered DNA methylation leads to targetable transcriptional plasticity in ATRT.Acta neuropathologica communications · 2025Article
- Development and validation of the Immune Profile Score (IPS), a novel multiomic algorithmic assay for stratifying outcomes in a real-world cohort of patients with advanced solid cancer treated with immune checkpoint inhibitors.Journal for immunotherapy of cancer · 2025Article
- Relative expression orderings based prediction of treatment response to Anti-PD-1 immunotherapy in advanced melanoma.Scientific reports · 2025Article
- The IFN-high phenotype: A biomarker-driven breakthrough in colorectal cancer treatment.Cell reports. Medicine · 2025Article
- Tumor-immune partitioning and clustering algorithm for identifying tumor-immune cell spatial interaction signatures within the tumor microenvironment.PLoS computational biology · 2025Article
- Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer.Journal of hematology & oncology · 2024Review
- Cell of origin alters myeloid-mediated immunosuppression in lung adenocarcinoma.bioRxiv : the preprint server for biology · 2024Article
- Insights into the prognostic value and immunological role of CD74 in pan-cancer.Discover oncology · 2024Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCadonilimab (AK104) is a first-in-class tetravalent bispecific antibody that targets both PD-1 and CTLA-4, showing a manageable safety profile and favorable clinical benefits. This study aimed to identify the biomarkers of clinical response and explore the immune response within the tumor microenvironment upon the AK104 therapy in advanced solid tumors. MATERIAL AND
methodsGene expression profiles of paired pre- and post-treatment tumor tissues from twenty-one patients were analyzed. The association of gene expression levels with either clinical efficacy or prognosis was evaluated and subsequently validated with published datasets using log-rank for Kaplan-Meier estimates. Comparative immune profile analyses of tumor microenvironment before and after AK104 treatment were conducted. The visualization of tumor-infiltrating lymphocytes was performed using multiplex immunohistochemistry. The predictive value of CD74 was further validated with protein expression by immunohistochemistry.
resultsBaseline CD74 gene expression was associated with favorable patient outcomes (overall survival [OS], HR = 0.33, 95% CI 0.11-1.03, p = 0.0463), which was further confirmed with the published datasets. Tumors with high CD74 gene expression at baseline were more likely to exhibit an immune-inflamed microenvironment. AK104 efficiently enhanced the infiltration of immune cells in the tumor microenvironment. Additionally, high CD74 protein expression (≥ 10% of the tumor area occupied by CD74 stained immune cells) at baseline was associated with better progressive-free survival (HR = 0.21, 95% CI 0.06-0.68, p = 0.0065) and OS (HR = 0.35, 95% CI 0.12-1.08, p = 0.0615).
conclusionsOur findings demonstrate that CD74 is a promising predictive biomarker for AK104 therapeutic response in advanced solid tumors. Trial registration number NCT03261011.
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