ReviewPharmacology & therapeutics2021
Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint.
Review in Pharmacology & therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
172 citing papers in PubMed, 3 syntheses or guidelines pooled it, 254 citations in OpenAlex.
- Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- sCD40 and sCD40L as candidate biomarkers of rheumatic diseases: a systematic review and meta-analysis with meta-regression.Frontiers in immunology · 2025Pooled it
- Transcriptomic datasets of cancer patients treated with immune-checkpoint inhibitors: a systematic review.Journal of translational medicine · 2022Pooled it
- Oncolytic virus encoding decorin and the CD40 ligand boosts T-cell response and achieves a durable antitumor response during breast cancer treatment.Molecular biomedicine · 2026Article
- Molecular Architecture and Clinical Landscape of Immune Checkpoint Receptors and Ligands.Antibodies (Basel, Switzerland) · 2026Review
- CMTM6 maintains B cell-intrinsic membrane CD40 stability to regulate anti-tumor immunity.Acta pharmaceutica Sinica. B · 2026Article
- Article
- Mechanism of Modified Shenqi Pill in Treatment of Allergic Rhinitis Comorbid with Asthma Based on Proteomics.Chinese journal of integrative medicine · 2026Article
- Unraveling the molecular evolution and immune functions of Lr-CD40 in Lethenteron reissneri.Fish physiology and biochemistry · 2026Article
- CD40 Agonist Therapy in Melanoma: Translating Preclinical Promise Into Clinical Practice.Pigment cell & melanoma research · 2026Review
- Trimerization of CD40L-specific affibody molecules using collagen domains enhances target binding and CD40 blockade.Cellular and molecular life sciences : CMLS · 2026Article
- Targeting CD4⁺ T cell infiltration: mechanisms and therapeutic insights into CD4⁺ T cell transmigration across the blood-brain barrier in acute ischemic stroke.Fluids and barriers of the CNS · 2026Review
- When the Liver Flares: Inflammatory and Immunometabolic Mechanisms Driving the Transition from MASLD to MASH.Inflammation · 2026Review
- CD40LG/CD28-Mediated Rho GTPase Signaling Drives Survival and Chemoresistance in Non-ETP T-ALL.International journal of molecular sciences · 2026Article
- Engineering a safe and potent LNP-mRNA delivery system by leveraging the dual activities of α-tocopherol.International journal of pharmaceutics: X · 2026Article
- The Relationship and Mechanism of CD27 with Coronary Atherosclerotic Heart Disease.Cardiovascular drugs and therapy · 2026Review
- Identification and validation of a prognostic risk-scoring model in drug-resistant ALL and evaluation of immune micro-environment.Annals of hematology · 2026Article
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- Proteome-wide Mendelian randomization identifies protein associations and therapeutic targets for B-cell malignancy.Blood neoplasia · 2026Article
- Systemic immune-inflammatory index predicts all-cause and cardiovascular mortality in metabolic syndrome: A prospective cohort study using NHANES data.Clinics (Sao Paulo, Brazil) · 2026Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The CD40 receptor and its ligand CD40L is one of the most critical molecular pairs of the stimulatory immune checkpoints. Both CD40 and CD40L have a membrane form and a soluble form generated by proteolytic cleavage or alternative splicing. CD40 and CD40L are widely expressed in various types of cells, among which B cells and myeloid cells constitutively express high levels of CD40, and T cells and platelets express high levels of CD40L upon activation. CD40L self-assembles into functional trimers which induce CD40 trimerization and downstream signaling. The canonical CD40/CD40L signaling is mediated by recruitment of TRAFs and NF-κB activation, which is supplemented by signal pathways such as PI3K/AKT, MAPKs and JAK3/STATs. CD40/CD40L immune checkpoint leads to activation of both innate and adaptive immune cells via two-way signaling. CD40/CD40L interaction also participates in regulating thrombosis, tissue inflammation, hematopoiesis and tumor cell fate. Because of its essential role in immune activation, CD40/CD40L interaction has been regarded as an attractive immunotherapy target. In recent years, significant advance has been made in CD40/CD40L-targeted therapy. Various types of agents, including agonistic/antagonistic monoclonal antibodies, cellular vaccines, adenoviral vectors and protein antagonist, have been developed and evaluated in early-stage clinical trials for treating malignancies, autoimmune diseases and allograft rejection. In general, these agents have demonstrated favorable safety and some of them show promising clinical efficacy. The mechanisms of benefits include immune cell activation and tumor cell lysis/apoptosis in malignancies, or immune cell inactivation in autoimmune diseases and allograft rejection. This review provides a comprehensive overview of the structure, processing, cellular expression pattern, signaling and effector function of CD40/CD40L checkpoint molecules. In addition, we summarize the progress, targeted diseases and outcomes of current ongoing and completed clinical trials of CD40/CD40L-targeted therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.