ArticleEMBO molecular medicine2019
Functional systemic CD4 immunity is required for clinical responses to PD-L1/PD-1 blockade therapy.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 4 of them syntheses that pooled it.
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The trial behind it
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Who cites it
139 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies.Molecular cancer · 2024Pooled it
- Medical Treatment of Lung Cancer: Can Immune Cells Predict the Response? A Systematic Review.Frontiers in immunology · 2020Pooled it
- Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer.Frontiers in immunology · 2020Pooled it
- A Systematic Review and Meta-Analysis of Immune-Related Adverse Events of Anti-PD-1 Drugs in Randomized Controlled Trials.Technology in cancer research & treatmentPooled it
- Phase II study of olaparib and durvalumab in patients with metastatic castration-resistant prostate cancer.Journal for immunotherapy of cancer · 2026Trial
- Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR-mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis.Clinical and translational medicine · 2025Trial
- Epigenetic priming enhances antitumor immunity in platinum-resistant ovarian cancer.The Journal of clinical investigation · 2022Trial
- Greater extent of blood-tumor TCR repertoire overlap is associated with favorable clinical responses to PD-1 blockade.Cancer science · 2021Trial
- A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma.Nature medicine · 2020Trial
- Combined Anti-PD-1/PD-L1 and Anti-angiogenic Therapy: An Emerging Direction for Future NSCLC Treatment.Current treatment options in oncology · 2026Review
- PD-1 regulates CD4Nature communications · 2026Article
- In vitro characterization of a bispecific anti-(PD-1/CTLA-4) single-chain diabody for cancer immunotherapy.Scientific reports · 2026Article
- Clinical significance of CD27Journal of ovarian research · 2026Article
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- CD4Cancer biology & medicine · 2026Review
- Peripheral blood immune profiling reveals key signatures in newly diagnosed NK/T cell lymphoma patients.Theranostics · 2026Article
- Comparative analysis of malignant pleural effusion and peripheral blood reveals unique T cell signatures associated with survival in mesothelioma patients.Oxford open immunology · 2026Article
- Increased Expression of HLA-DR and CD69 on Peripheral CD4ImmunoTargets and therapy · 2026Article
- Single-cell RNA sequencing: enhancing the predictive accuracy of tumor immunotherapy efficacy.Essays in biochemistry · 2025Review
- Beyond the tumor microenvironment: Orchestrating systemic T‑cell response for next‑generation cancer immunotherapy (Review).International journal of oncology · 2025Review
79 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
The majority of lung cancer patients progressing from conventional therapies are refractory to PD-L1/PD-1 blockade monotherapy. Here, we show that baseline systemic CD4 immunity is a differential factor for clinical responses. Patients with functional systemic CD4 T cells included all objective responders and could be identified before the start of therapy by having a high proportion of memory CD4 T cells. In these patients, CD4 T cells possessed significant proliferative capacities, low co-expression of PD-1/LAG-3 and were responsive to PD-1 blockade ex vivo and in vivo. In contrast, patients with dysfunctional systemic CD4 immunity did not respond even though they had lung cancer-specific T cells. Although proficient in cytokine production, CD4 T cells in these patients proliferated very poorly, strongly co-upregulated PD-1/LAG-3, and were largely refractory to PD-1 monoblockade. CD8 immunity only recovered in patients with functional CD4 immunity. T-cell proliferative dysfunctionality could be reverted by PD-1/LAG-3 co-blockade. Patients with functional CD4 immunity and PD-L1 tumor positivity exhibited response rates of 70%, highlighting the contribution of CD4 immunity for efficacious PD-L1/PD-1 blockade therapy.
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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.