ArticleBlood2012
Polyfunctional CD4⁺ T cells are essential for eradicating advanced B-cell lymphoma after chemotherapy.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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
53 citing papers in PubMed, 81 citations in OpenAlex.
- Influence of polyfunctional TbetFrontiers in immunology · 2025Trial
- Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma.Cancer research · 2018Trial
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- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- Epigenetic reprogramming of T cell metabolism restores function and enhances anti-tumor immunity in lung cancer.Nature immunology · 2026Article
- A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications.Molecular therapy. Methods & clinical development · 2024Article
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- How lactate affects immune strategies in lymphoma.Frontiers in molecular biosciences · 2024Review
- Neoantigen-specific CD4Journal for immunotherapy of cancer · 2023Article
- Targeting KRASFrontiers in immunology · 2023Article
- Regulatory and effector T cell subsets in tumor-draining lymph nodes of patients with squamous cell carcinoma of head and neck.BMC immunology · 2022Article
- Indomethacin-induced oxidative stress enhances death receptor 5 signaling and sensitizes tumor cells to adoptive T-cell therapy.Journal for immunotherapy of cancer · 2022Article
- Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VIII: CAR-T cells: preclinical development - Safety and efficacy evaluation.Hematology, transfusion and cell therapy · 2021Article
- A novel prognostic signature based on immune-related genes of diffuse large B-cell lymphoma.Aging · 2021Article
- Epigenetic modulation of immune synaptic-cytoskeletal networks potentiates γδ T cell-mediated cytotoxicity in lung cancer.Nature communications · 2021Article
- Review
- Article
- Persistent STAT5 activation reprograms the epigenetic landscape in CD4Science immunology · 2020Article
- Polymorphic Region-Specific Antibody for Evaluation of Affinity-Associated Profile of Chimeric Antigen Receptor.Molecular therapy oncolytics · 2020Article
- A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy.Oncoimmunology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The finding that many chemotherapeutic agents have immunostimulatory effects has provided the impetus to combine chemotherapy and immunotherapy for synergistic antitumor effects. However, the critical determinants of effective antitumor immunity after chemotherapy have not been defined. Here we report that adoptive transfer of tumor-specific CD4⁺ T cells after chemotherapy with cyclophosphamide gave rise to polyfunctional CD4⁺ effector cells, which in turn intensified the inflammatory milieu and enhanced the activation of CD8⁺ T cells in the tumor microenvironment. Although this combined chemoimmunotherapy initially resulted in progressive regression of advanced B-cell lymphoma, its therapeutic efficacy was not durable and most mice succumbed to late relapse. Notably, relapse was associated with acquisition of a tolerized phenotype in tumor-specific CD4⁺ T cells, characterized by overexpression of program death-1 (PD-1). Remarkably, effective antitumor immunity was maintained and cure became prevalent when polyfunctional CD4⁺ effector cells were prevented from undergoing PD-1-mediated tolerization, either by antibody blockade of the PD-1-PD-L1 pathway, or targeted ablation of PD-1 in tumor-specific CD4⁺ T cells. Our study suggests that tumor-reactive CD4⁺ T cells act as the "gatekeepers" of the host antitumor immunity in the postchemotherapy setting, thereby their functional status governs the choice between eradication versus regrowth of residual tumors.
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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.