ArticleCancer immunology, immunotherapy : CII2025
CD40 transcriptomic expression patterns across malignancies: implications for clinical trials of CD40 agonists.
Article in Cancer immunology, immunotherapy : CII, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- T‑Cell Immunoreceptor with Ig and Immunoreceptor Tyrosine-Based Inhibitory Motif Domains/Cluster of Differentiation 40 Cellular Nanovesicles Carrying Oxaliplatin Exhibited Superior Pancreatic Cancer Cells Therapy.ACS pharmacology & translational science · 2026Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundCD40 is a T-cell co-stimulatory receptor targeted by next-generation immunotherapies. We conducted a pan-cancer transcriptome analysis of CD40, its ligand, and related immune markers to evaluate co-expression patterns and clinical outcomes.
methodsWe analyzed transcriptome data for CD40, its ligand, and other common checkpoints and co-stimulators (PD-1, PD-L1, PD-L2, CTLA-4, LAG-3, ICOS, CD27, CD28, OX40, and GITR). RNA expression was classified as high (75-100th percentile), moderate (25-74th), or low (0-24th) against a reference population of 735 previously tested solid tumors.
resultsOf 514 patients, 114 (22%) showed high, 247 (48%) moderate, and 153 (30%) low CD40 RNA expression. High CD40 expression was most frequent in liver and bile duct (42%), pancreatic (42%), and ovarian (40%) cancers. Both high CD40 and low-moderate CD40 ligand expression-potentially conducive to CD40 agonist therapy-was most frequent in ovarian (33%) and pancreatic (24%) cancer. In both UCSD (N = 514) and TCGA (N = 10,953) cohorts, high CD40 expression significantly correlated with high CD28 and GITR. High CD40 RNA levels were not prognostic for overall survival (OS) from metastatic disease (P = 0.2) (n = 272 immune checkpoint inhibitor (ICI)-naïve patients). High CD40 expression correlated with longer OS from immunotherapy initiation (n = 217 ICI-treated patients; P = 0.04, univariable analysis), but not multivariable analysis, suggesting it may not be an independent predictive biomarker.
conclusionHigh CD40 expression correlated with liver and bile duct, pancreatic, and ovarian cancers, as well as with CD28 and GITR transcripts. Immune marker co-expression in individual patients merits further exploration for the development of CD40-based and other immunotherapy interventions.
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