ArticleThe Journal of experimental medicine2024
Anti-PD-1 therapy triggers Tfh cell-dependent IL-4 release to boost CD8 T cell responses in tumor-draining lymph nodes.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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
30 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Tumor-specific antibodies elicited by engineered bacteria promote bladder cancer immunotherapy in preclinical mouse models.Science translational medicine · 2026Article
- Incidence of B-cell Malignancies in Patients with Lung Cancer Receiving PD-1 Blockade Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Anti-PD-1 single-chain variable fragments in cancer immunotherapy: from molecular engineering to clinical translation.Cancer chemotherapy and pharmacology · 2026Review
- Lymph node fine-tuning FcγR signaling boosts anti-PD-1 therapy.Journal for immunotherapy of cancer · 2026Article
- Humanized and Charge-Optimized CSPG4-Specific CAR-T Cells show Enhanced Efficacy against Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- T-Cell Immunity and Lung Cancer.Respirology (Carlton, Vic.) · 2026Review
- Blood Based Biomarkers for Predicting Treatment Response to Immune Checkpoint Inhibitors After EGFR-TKI Resistance in Non-Small Cell Lung Cancer.Thoracic cancer · 2026Article
- γδ T cell-derived IL-4 initiates CD8Nature immunology · 2026Article
- Neoadjuvant modified FOLFIRINOX plus nivolumab in borderline-resectable pancreatic ductal adenocarcinoma: a pilot phase 1 trial.Nature communications · 2026Article
- Activated Lymphocyte-Based Immunotherapy Plus Tomotherapy in an Older Patient with Stage III Lung Cancer: A Case Report.Geriatrics (Basel, Switzerland) · 2026Article
- Noninvasive in vivo deoxycytidine kinase (dCK)-PET identifies tumor-draining lymph nodes upon immune checkpoint inhibitor therapy.Npj imaging · 2026Article
- Follicular T cells in the ovarian cancer immune microenvironment: biological insights and translational implications.Frontiers in immunology · 2026Review
- Beyond density: mapping the functional landscapes of macrophage-T lymphocyte niches in the tumor microenvironment.Frontiers in immunology · 2026Review
- Temporal association of diffuse large B-cell lymphoma with PD-1 inhibitor therapy in a patient with gastric adenocarcinoma: a case report.Frontiers in immunology · 2026Article
- Combined CD25-targeted near infrared photoimmunotherapy (NIR-PIT) and intratumor IL-15 enhance the effectiveness of anti-PD-1 immunotherapy.Cancer immunology, immunotherapy : CII · 2025Article
- Review
- Polio virotherapy provokes MDA5 signaling and CD4Microbiology and molecular biology reviews : MMBR · 2025Review
- High baseline PD-1+ CD8 T Cells and TIGIT+ CD8 T Cells in circulation associated with response to PD-1 blockade in patients with non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Anti-PD-1 therapy targets intratumoral CD8+ T cells to promote clinical responses in cancer patients. Recent evidence suggests an additional activity in the periphery, but the underlying mechanism is unclear. Here, we show that anti-PD-1 mAb enhances CD8+ T cell responses in tumor-draining lymph nodes by stimulating cytokine production in follicular helper T cells (Tfh). In two different models, anti-PD-1 mAb increased the activation and proliferation of tumor-specific T cells in lymph nodes. Surprisingly, anti-PD-1 mAb did not primarily target CD8+ T cells but instead stimulated IL-4 production by Tfh cells, the major population bound by anti-PD-1 mAb. Blocking IL-4 or inhibiting the Tfh master transcription factor BCL6 abrogated anti-PD-1 mAb activity in lymph nodes while injection of IL-4 complexes was sufficient to recapitulate anti-PD-1 mAb activity. A similar mechanism was observed in a vaccine model. Finally, nivolumab also boosted human Tfh cells in humanized mice. We propose that Tfh cells and IL-4 play a key role in the peripheral activity of anti-PD-1 mAb.
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.