ArticleJCI insight2020
CCL5 mediates CD40-driven CD4+ T cell tumor infiltration and immunity.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 124 citations in OpenAlex.
- Systemic inflammation is a determinant of outcomes of CD40 agonist-based therapy in pancreatic cancer patients.JCI insight · 2021Trial
- CD40 agonism in renal cell carcinoma enhances immune checkpoint activity through myeloid cells.iScience · 2026Article
- Enhancing CAR-T Cell Efficacy in Solid Tumors by Inhibiting CCL5/VEGF-Mediated Angiogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reprogramming T cell-myeloid crosstalk overcomes immune resistance in colorectal cancer.Cell reports. Medicine · 2026Article
- Harnessing Inflammatory Monocytes to Overcome Resistance to Anti-PD-1 Immunotherapy.bioRxiv : the preprint server for biology · 2026Article
- Joint modeling of cellular heterogeneity and condition effects with scPCA in single-cell RNA-seq.Communications biology · 2026Article
- Agonistic CD40 elicits CD8+ T-cell-dependent primary responses and CD4+ T-cell-dependent long-term immunity in breast cancer.NPJ breast cancer · 2026Article
- A Combinatorial Effect of Immune Checkpoint Inhibitors and CD40 Agonistic Antibody in Murine Pancreatic Cancer Model.Cancer science · 2026Article
- The effect of CD40 agonist antibody therapy on the pancreatic cancer microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Single-cell resolution spatial analysis of antigen-presenting cancer-associated fibroblast niches.Cancer cell · 2025Article
- Targeting neoantigens conserved across organs and species overcomes tumor immune escape.bioRxiv : the preprint server for biology · 2025Article
- Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy.Science advances · 2025Article
- IgG autoantibodies in bullous pemphigoid induce a pathogenic MyD88-dependent pro-inflammatory response in keratinocytes.Nature communications · 2025Article
- Facts and Hopes of CD40 Agonists in Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Tumor and α-SMA-expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade.Molecular oncology · 2025Article
- Chemokines that govern T cell activity in tumors.Current opinion in immunology · 2025Review
- Allogeneic DNT cell therapy synergizes with T cells to promote anti-leukemic activities while suppressing GvHD.Journal of experimental & clinical cancer research : CR · 2025Article
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- Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction.Frontiers in immunology · 2025Review
23 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
5 authors at 1 institution in 1 country.
Funding
Abstract
The role CD4+ T cells play in tumor immunity is less well appreciated than the cytotoxic role of CD8+ T cells. Despite clear evidence for CD4+ T cell dependency across multiple immunotherapies, the mechanisms by which CD4+ T cells infiltrate tumors remain poorly understood. Prior studies by our group have shown in a mouse model of pancreatic cancer that systemic activation of the cell surface TNF superfamily member CD40 drives T cell infiltration into tumors and, in combination with immune checkpoint blockade, leads to durable tumor regressions and cures that depend on both CD8+ and CD4+ T cells. Here, we used single-cell transcriptomics to examine the tumor microenvironment following treatment with agonist CD40 antibody with or without immune checkpoint blockade. We show that intratumor myeloid cells produce the chemokine CCL5 in response to CD40 agonist and that CCL5 mediates an influx of CD4+ T cells into the tumor microenvironment. Disruption of CCL5 genetically or pharmacologically mitigates the influx of CD4+ but not CD8+ T cells into tumors and blunts the therapeutic efficacy of immunotherapy. These findings highlight a previously unappreciated role for CCL5 in selectively mediating CD4+ T cell tumor infiltration in response to effective immunotherapy.
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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.