ArticleJCI insight2021
PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1hiCD39+ CD4 T cells.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05867004 (Blocking TNF to Potentiate the ICI-dependent Immune Awakening in Melanoma), which is not on this map. Cited by 108 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.
Blocking TNF to Potentiate the ICI-dependent Immune Awakening in Melanoma
Who cites it
108 citing papers in PubMed, 136 citations in OpenAlex.
- CD39 on CD8European journal of immunology · 2026Review
- A homozygous CTLA-4 variant causes CTLA-4 deficiency with severe immune dysregulation.Journal of human immunity · 2026Article
- The multifaceted landscape of T cell exhaustion in organ transplantation: From molecular mechanisms (epigenetics, transcription, metabolism) to induction strategies.Genes & diseases · 2026Review
- PD-1 regulates CD4Nature communications · 2026Article
- Exploration of the protein and pharmacological landscape of monkeypox virus treatment: from entry point to end point.Molecular diversity · 2026Review
- Article
- 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 Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Exhausted T cell phenotypes in disseminated coccidioidomycosis.JCI insight · 2026Article
- From guardians to traitors: molecular mechanisms of tumor-induced T cell betrayal.Molecular cancer · 2026Review
- Terminal T-cell exhaustion predicts tumor control independent of immunotherapy in ovarian cancer.NPJ precision oncology · 2026Article
- Drug-free Immunotherapeutic Biomimetic Nanoparticles for Treating Triple-Negative Breast Cancer.ACS nano · 2026Article
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- CD4Cancer biology & medicine · 2026Review
- Efficacy of FOXP3+Treg cells combined with platelet in predicting recurrence of cervical cancer: a retrospective study.BMC women's health · 2026Article
- Stepwise differentiation from precursor intermediates and distinct Th1 checkpoints promote CD4 Th1 cell differentiation during chronic viral infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Exhausted T cell phenotypes in disseminated coccidioidomycosis.medRxiv : the preprint server for health sciences · 2026Article
- Partial-EMT in oral squamous cell carcinoma: molecular circuitry and clinical translation.International journal of oral science · 2026Review
- Genital herpes shedding episodes associate with altered spatial organization and activation of mucosal immune cells.JCI insight · 2026Article
- Immunotherapeutic potential of PD-1 blockade in chronic Leishmania mexicana infection through the enhancement of progenitor-like CXCR5Frontiers in immunology · 2026Article
48 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
21 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor antigen-specific CD4 T cells accumulate at tumor sites, evoking their involvement in antitumor effector functions in situ. Contrary to CD8 cytotoxic T lymphocyte exhaustion, that of CD4 T cells remains poorly appreciated. Here, using phenotypic, transcriptomic, and functional approaches, we characterized CD4 T cell exhaustion in patients with head and neck, cervical, and ovarian cancer. We identified a CD4 tumor-infiltrating lymphocyte (TIL) population, defined by high PD-1 and CD39 expression, which contained high proportions of cytokine-producing cells, although the quantity of cytokines produced by these cells was low, evoking an exhausted state. Terminal exhaustion of CD4 TILs was instated regardless of TIM-3 expression, suggesting divergence with CD8 T cell exhaustion. scRNA-Seq and further phenotypic analyses uncovered similarities with the CD8 T cell exhaustion program. In particular, PD-1hiCD39+ CD4 TILs expressed the exhaustion transcription factor TOX and the chemokine CXCL13 and were tumor antigen specific. In vitro, PD-1 blockade enhanced CD4 TIL activation, as evidenced by increased CD154 expression and cytokine secretion, leading to improved dendritic cell maturation and consequently higher tumor-specific CD8 T cell proliferation. Our data identify exhausted CD4 TILs as players in responsiveness to immune checkpoint blockade.
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.