ReviewFrontiers in immunology2014
How Do CD4(+) T Cells Detect and Eliminate Tumor Cells That Either Lack or Express MHC Class II Molecules?
Review in Frontiers in immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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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.
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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
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- The Expression and Survival Significance of FOXD1 in Lung Squamous Cell Carcinoma: A Meta-Analysis, Immunohistochemistry Validation, and Bioinformatics Analysis.BioMed research international · 2022Pooled it
- Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma.Nature communications · 2021Trial
- Evaluation of T-Cell Responses Against Shared Melanoma Associated Antigens and Predicted Neoantigens in Cutaneous Melanoma Patients Treated With the CSF-470 Allogeneic Cell Vaccine Plus BCG and GM-CSF.Frontiers in immunology · 2020Trial
- Molecular origin, discovery, validation and application of neoantigens.Asian journal of pharmaceutical sciences · 2026Review
- Efficacy and safety of CTLA-4, PD-1 and LAG-3 immune checkpoint inhibitors as monotherapy and combination therapy in advanced melanoma: A systematic review and meta-analysis.EXCLI journal · 2026Review
- In Silico Development of a Multi-epitope Vaccine Targeting TFDP3: A Novel Approach for Cancer Immunotherapy.Cell biochemistry and biophysics · 2025Article
- Mendelian Randomization Combined with Bioinformatics Revealed Specific Allergy-Mediated Protective Mechanisms Against Renal Cell Carcinoma.Phenomics (Cham, Switzerland) · 2025Article
- Crosstalk between autophagy and apoptosis in initiating antitumor immune responses in human lymphoma cells.Exploration of immunology · 2025Article
- Asterias amurensis lipids enhance the immunity of immunosuppressed mice as sustainable marine-eco materials.Scientific reports · 2025Article
- Unique transcriptomic responses of rat and human alveolar macrophages in an in vitro model of overload with TiOParticle and fibre toxicology · 2025Article
- Closer proximity of pre-treatment CD4Translational lung cancer research · 2025Article
- Potentiating CAR-T cell function in the immunosuppressive tumor microenvironment by inverting the TGF-β signal.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- DNA-PKcs Dysfunction Enhances the Antitumor Activity of Radioimmunotherapy by Activating the cGAS-STING Pathway in HNSCC.Journal of inflammation research · 2025Article
- Cancer vaccines: an update on recent achievements and prospects for cancer therapy.Clinical and experimental medicine · 2024Review
- Therapeutic activity of retroviral replicating vector-mediated gene therapy in combination with anti-PD-1 antibody in a murine pancreatic cancer model.Cancer gene therapy · 2024Article
- Antimelanoma Effects ofDiseases (Basel, Switzerland) · 2024Article
- Prognostic role of macrophages and mast cells in the microenvironment of hepatocellular carcinoma after resection.BMC cancer · 2024Article
- Characterization of atypical T cells generated duringFrontiers in immunology · 2024Article
- Anti-CTLA-4 treatment suppresses hepatocellular carcinoma growth through Th1-mediated cell cycle arrest and apoptosis.PloS one · 2024Article
- A Wrinkle in TIME: How Changes in the Aging ECM Drive the Remodeling of the Tumor Immune Microenvironment.Cancer discovery · 2023Article
55 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
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4(+) T cells contribute to tumor eradication, even in the absence of CD8(+) T cells. Cytotoxic CD4(+) T cells can directly kill MHC class II positive tumor cells. More surprisingly, CD4(+) T cells can indirectly eliminate tumor cells that lack MHC class II expression. Here, we review the mechanisms of direct and indirect CD4(+) T cell-mediated elimination of tumor cells. An emphasis is put on T cell receptor (TCR) transgenic models, where anti-tumor responses of naïve CD4(+) T cells of defined specificity can be tracked. Some generalizations can tentatively be made. For both MHCII(POS) and MHCII(NEG) tumors, presentation of tumor-specific antigen by host antigen-presenting cells (APCs) appears to be required for CD4(+) T cell priming. This has been extensively studied in a myeloma model (MOPC315), where host APCs in tumor-draining lymph nodes are primed with secreted tumor antigen. Upon antigen recognition, naïve CD4(+) T cells differentiate into Th1 cells and migrate to the tumor. At the tumor site, the mechanisms for elimination of MHCII(POS) and MHCII(NEG) tumor cells differ. In a TCR-transgenic B16 melanoma model, MHCII(POS) melanoma cells are directly killed by cytotoxic CD4(+) T cells in a perforin/granzyme B-dependent manner. By contrast, MHCII(NEG) myeloma cells are killed by IFN-γ stimulated M1-like macrophages. In summary, while the priming phase of CD4(+) T cells appears similar for MHCII(POS) and MHCII(NEG) tumors, the killing mechanisms are different. Unresolved issues and directions for future research are addressed.
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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.