ArticleScience advances2021
Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
220 citing papers in PubMed, 1 synthesis or guideline pooled it, 308 citations in OpenAlex.
- Efficacy of Using Dendritic Cells in the Treatment of Prostate Cancer: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Dynamic immune profiling predicts response to radiation plus anti-PD-1 therapy in oligometastatic renal cell carcinoma.Nature communications · 2026Trial
- CXCL13-expressing CD4Oncoimmunology · 2026Article
- Gliadin-specific CD4Science advances · 2026Article
- Targeting BCL9/BCL9L enhances CD4Acta pharmacologica Sinica · 2026Article
- Local and circulating cytotoxic CD4medRxiv : the preprint server for health sciences · 2026Article
- Mutant KRAS peptide vaccine with dual checkpoint blockade in metastatic colorectal cancer: a phase I trial.Nature communications · 2026Article
- CD4Science (New York, N.Y.) · 2026Article
- Suppression of macrophage membrane cholesterol efflux by SLAMF7-induced IL-7 signaling improves immunotherapy efficacy in hepatocellular carcinoma.Hepatology international · 2026Article
- Epithelial-mesenchymal transition and immunosuppression: Two sides of the same coin.Cellular and molecular life sciences : CMLS · 2026Review
- CD4+ T Cells Sensitize Quasimesenchymal Breast Tumors Lacking CD73 to Anti-CTLA4 Immune Checkpoint Blockade Therapy.Cancer research communications · 2026Article
- An epigenetic switch in vascular phenotype augments anti-tumor immunity.Angiogenesis · 2026Article
- TOX drives CD4Nature immunology · 2026Article
- Biomimetic proteolipid vesicles delivering small activating RNA to activate the macrophage immunotherapy for the treatment of lung cancer.Journal of nanobiotechnology · 2026Article
- Limited protection against early-life lung murine cytomegalovirus infection results from deficiency of cytotoxic CD8 T cells.PLoS pathogens · 2026Article
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Mutant p53 epigenetically rewires CXCL10 to promote CD8⁺ T-cell infiltration and enhance the anti-PD-1 response in advanced prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Article
- Cytotoxic CD4 T Cells: Dual Agents in HIV-1 Pathogenesis and Persistence.Current HIV/AIDS reports · 2026Review
- Functionally Characterizing the Renal Cell Carcinoma Tumor-Immune Microenvironment via Patient-Derived Ex Vivo Models.Cancer research communications · 2026Article
160 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
25 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4 T cells have been implicated in cancer immunity for their helper functions. Moreover, their direct cytotoxic potential has been shown in some patients with cancer. Here, by mining single-cell RNA-seq datasets, we identified CD4 T cell clusters displaying cytotoxic phenotypes in different human cancers, resembling CD8 T cell profiles. Using the peptide-MHCII-multimer technology, we confirmed ex vivo the presence of cytolytic tumor-specific CD4 T cells. We performed an integrated phenotypic and functional characterization of these cells, down to the single-cell level, through a high-throughput nanobiochip consisting of massive arrays of picowells and machine learning. We demonstrated a direct, contact-, and granzyme-dependent cytotoxic activity against tumors, with delayed kinetics compared to classical cytotoxic lymphocytes. Last, we found that this cytotoxic activity was in part dependent on SLAMF7. Agonistic engagement of SLAMF7 enhanced cytotoxicity of tumor-specific CD4 T cells, suggesting that targeting these cells might prove synergistic with other cancer immunotherapies.
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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.