ArticleJournal of immunology (Baltimore, Md. : 1950)2015
CD4+ T Cell Help Selectively Enhances High-Avidity Tumor Antigen-Specific CD8+ T Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 43 citations in OpenAlex.
- Vaccination with cationic liposome-encapsulated CD4 and CD8 T cell neoepitopes induces superior tumor control.Materials today. Bio · 2026Article
- Could a COVID-19 vaccine improve the effectiveness of cancer immunotherapy?Nature reviews. Clinical oncology · 2026Article
- Lag3 and PD-1 pathways preferentially regulate NFAT-dependent TCR signalling programmes during early CD4Immunotherapy advances · 2025Article
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- Linked CD4+/CD8+ T cell neoantigen vaccination overcomes immune checkpoint blockade resistance and enables tumor regression.The Journal of clinical investigation · 2023Article
- In vitro and in vivo evaluation of DC-targeting PLGA nanoparticles encapsulating heparanase CD4Cancer immunology, immunotherapy : CII · 2022Article
- Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors.Nature communications · 2022Article
- Clinical and Translational Advances in Glioma Immunotherapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Immunotherapy: an alternative promising therapeutic approach against cancers.Molecular biology reports · 2022Review
- Antitumor Peptide-Based Vaccine in the Limelight.Vaccines · 2022Review
- Data-driven analysis to identify prognostic immune-related biomarkers in BRAF mutated cutaneous melanoma microenvironment.Frontiers in genetics · 2022Article
- Multiplexed imaging mass cytometry reveals distinct tumor-immune microenvironments linked to immunotherapy responses in melanoma.Communications medicine · 2022Article
- Article
- Natural Killer-Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy.Cancers · 2021Review
- Moving on From Sipuleucel-T: New Dendritic Cell Vaccine Strategies for Prostate Cancer.Frontiers in immunology · 2021Review
- Data mining of immune-related prognostic genes in metastatic melanoma microenvironment.Bioscience reports · 2020Article
- Adoptive T Cell Therapy with IL-12-Preconditioned Low-Avidity T Cells Prevents Exhaustion and Results in Enhanced T Cell Activation, Enhanced Tumor Clearance, and Decreased Risk for Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Enhancing the Efficacy of Tumor Vaccines Based on Immune Evasion Mechanisms.Frontiers in oncology · 2020Review
- Article
- The pursuit of transplantation tolerance: new mechanistic insights.Cellular & molecular immunology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Maintaining antitumor immunity remains a persistent impediment to cancer immunotherapy. We and others have previously reported that high-avidity CD8(+) T cells are more susceptible to tolerance induction in the tumor microenvironment. In the present study, we used a novel model where T cells derived from two independent TCR transgenic mouse lines recognize the same melanoma antigenic epitope but differ in their avidity. We tested whether providing CD4(+) T cell help would improve T cell responsiveness as a function of effector T cell avidity. Interestingly, delivery of CD4(+) T cell help during in vitro priming of CD8(+) T cells improved cytokine secretion and lytic capacity of high-avidity T cells, but not low-avidity T cells. Consistent with this observation, copriming with CD4(+) T cells improved antitumor immunity mediated by higher avidity, melanoma-specific CD8(+) T cells, but not T cells with similar specificity but lower avidity. Enhanced tumor immunity was associated with improved CD8(+) T cell expansion and reduced tolerization, and it was dependent on presentation of both CD4(+) and CD8(+) T cell epitopes by the same dendritic cell population. Our findings demonstrate that CD4(+) T cell help preferentially augments high-avidity CD8(+) T cells and provide important insight for understanding the requirements to elicit and maintain durable tumor immunity.
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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.