ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Restoring immune function of tumor-specific CD4+ T cells during recurrence of melanoma.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
What it found
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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.
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
125 citing papers in PubMed, 207 citations in OpenAlex.
- Prognostic Impact and Clinicopathological Significance of TIM-3 and LAG-3 Expressions in Laryngeal Squamous Cell Carcinoma.Laryngoscope investigative otolaryngology · 2026Article
- Dysfunctional CD4 T cells in an oncovirus-specific TCR-transgenic in vivo model.Nature communications · 2025Article
- Sustained and specific multiplexed immune checkpoint modulation in CAR T cells induced by targeted epigenome editing.Molecular therapy. Nucleic acids · 2025Article
- Development of therapeutic cancer vaccines based on cancer immunity cycle.Frontiers of medicine · 2025Review
- LAG3 regulates antibody responses in a murine model of kidney transplantation.The Journal of clinical investigation · 2025Article
- The response to anti-PD-1 and anti-LAG-3 checkpoint blockade is associated with regulatory T cell reprogramming.Science translational medicine · 2025Article
- Nanobodies as innovative immune checkpoint modulators: advancing cancer immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Research progress and challenges of the PD-1/PD-L1 axis in gliomas.Cell & bioscience · 2024Review
- Deciphering CD4Molecular carcinogenesis · 2024Review
- Molecular and transcriptional basis of bidirectional CD4MedComm · 2024Article
- Progress of lymphocyte activation gene 3 and programmed cell death protein 1 antibodies for cancer treatment: A review.Biomolecules & biomedicine · 2024Review
- Promising immunotherapy targets: TIM3, LAG3, and TIGIT joined the party.Molecular therapy. Oncology · 2024Review
- Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma.Molecular cancer · 2024Article
- Protocol for Efficient Generation of Chimeric Antigen Receptor T Cells with Multiplexed Gene Silencing by Epigenome Editing.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Identification of KIFC1 as an independent prognostic marker in renal clear cell carcinoma correlates with tumor proliferation and immune infiltration.Scientific reports · 2023Article
- Neoantigen-specific CD4Journal for immunotherapy of cancer · 2023Article
- Review
- The role of CD4MedComm · 2023Review
- Dynamic single-cell mapping unveils Epstein‒Barr virus-imprinted T-cell exhaustion and on-treatment response.Signal transduction and targeted therapy · 2023Article
- Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.Journal of hematology & oncology · 2023Review
65 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
10 authors at 5 institutions in 4 countries.
Funding
Abstract
Recurrent solid malignancies are often refractory to standard therapies. Although adoptive T cell transfer may benefit select individuals, the majority of patients succumb to their disease. To address this important clinical dilemma, we developed a mouse melanoma model in which initial regression of advanced disease was followed by tumor recurrence. During recurrence, Foxp3(+) tumor-specific CD4(+) T cells became PD-1(+) and represented >60% of the tumor-specific CD4(+) T cells in the host. Concomitantly, tumor-specific CD4(+) T effector cells showed traits of chronic exhaustion, as evidenced by their high expression of the PD-1, TIM-3, 2B4, TIGIT, and LAG-3 inhibitory molecules. Although blockade of the PD-1/PD-L1 pathway with anti-PD-L1 Abs or depletion of tumor-specific regulatory T cells (Tregs) alone failed to reverse tumor recurrence, the combination of PD-L1 blockade with tumor-specific Treg depletion effectively mediated disease regression. Furthermore, blockade with a combination of anti-PD-L1 and anti-LAG-3 Abs overcame the requirement to deplete tumor-specific Tregs. In contrast, successful treatment of primary melanoma with adoptive cell therapy required only Treg depletion or Ab therapy, underscoring the differences in the characteristics of treatment between primary and relapsing cancer. These data highlight the need for preclinical development of combined immunotherapy approaches specifically targeting recurrent disease.
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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.