ArticleImmunology and cell biology2016
Tumour-specific CD4 T cells eradicate melanoma via indirect recognition of tumour-derived antigen.
Article in Immunology and cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- Why CD4+ T cells matter in adoptive cell therapy for solid cancers.Immuno-oncology technology · 2026Review
- Antimelanoma Effects ofDiseases (Basel, Switzerland) · 2024Article
- MHCII restriction demonstrates B cells have very limited capacity to activate tumour-specific CD4Oncoimmunology · 2024Article
- Methionine consumption by cancer cells drives a progressive upregulation of PD-1 expression in CD4 T cells.Nature communications · 2023Article
- Systemic CD4 Immunity and PD-L1/PD-1 Blockade Immunotherapy.International journal of molecular sciences · 2022Review
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- Tailoring biomaterials and applications targeting tumor-associated macrophages in cancers.Frontiers in immunology · 2022Review
- A phase I/II escalation trial design T-RAD: Treatment of metastatic lung cancer with mRNA-engineered T cells expressing a T cell receptor targeting human telomerase reverse transcriptase (hTERT).Frontiers in oncology · 2022Article
- Roles of CD4+ T cells as mediators of antitumor immunity.Frontiers in immunology · 2022Review
- Core immune cell infiltration signatures identify molecular subtypes and promote precise checkpoint immunotherapy in cutaneous melanoma.Frontiers in immunology · 2022Article
- MHC Class I Deficiency in Solid Tumors and Therapeutic Strategies to Overcome It.International journal of molecular sciences · 2021Review
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- Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Interleukin-33 modulates immune responses in cutaneous melanoma in a context-specific way.Aging · 2021Article
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- Systemic CD4 Immunity as a Key Contributor to PD-L1/PD-1 Blockade Immunotherapy Efficacy.Frontiers in immunology · 2020Review
- CD4Cancer immunology, immunotherapy : CII · 2019Review
- Cognate Interaction With CD4Frontiers in immunology · 2019Article
- Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The importance of CD4 T cells in tumour immunity has been increasingly recognised, with recent reports describing robust CD4 T cell-dependent tumour control in mice whose immune-regulatory mechanisms have been disturbed by irradiation, chemotherapy, immunomodulatory therapy and/or constitutive immunodeficiency. Tumour control in such models has been attributed in large part to direct Major Histocompatibility Complex (MHC) class II-dependent CD4 T cell killing of tumour cells. To test whether CD4 T cells can eradicate tumours without directly killing tumour cells, we developed an animal model in which tumour-derived antigen could be presented to T-cell receptor (TCR)-transgenic CD4 T cells by host but not tumour MHC class II molecules. In I-E(+) mice bearing I-E(null) tumours, naive I-E-restricted CD4 T cells proliferated locally in tumour-draining lymph nodes after recognising tumour-derived antigen on migratory dendritic cells. In lymphopaenic but not immunosufficient hosts, CD4 T cells differentiated into polarised T helper type 1 (Th1) cells expressing interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα) and interleukin (IL)-2 but little IL-17, and cleared established tumours. Tumour clearance was enhanced by higher TCR affinity for tumour antigen-MHC class II and was critically dependent on IFNγ, as demonstrated by early tumour escape in animals treated with an IFNγ blocking antibody. Thus, CD4 T cells and IFNγ can control tumour growth without direct T-cell killing of tumour cells, and without requiring additional adaptive immune cells such as CD8 T cells and B cells. Our results support a role for effective CD4 T cell-dependent tumour immunity against MHC class II-negative tumours.
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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.