ReviewClinical cancer research : an official journal of the American Association for Cancer Research2021
CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?
Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.
What it found
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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
163 citing papers in PubMed, 225 citations in OpenAlex.
- Effects of Bojungikki-Tang on immune response and clinical outcomes in NSCLC patients receiving immune checkpoint inhibitors: a randomized pilot study.BMC cancer · 2025Trial
- Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients.Frontiers in immunology · 2021Trial
- Exploring the feasibility of exercise training during (neo)adjuvant chemotherapy in women with early-stage breast cancer: a pilot study examining immune and metabolic outcomes.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Article
- Engineered probiotics for tumor-targeted combination chemoimmunotherapy.Science translational medicine · 2026Article
- The multifaceted landscape of T cell exhaustion in organ transplantation: From molecular mechanisms (epigenetics, transcription, metabolism) to induction strategies.Genes & diseases · 2026Review
- Paradoxical Th1 activation and CTLA-4 regulation is beneficial during latent cryptococcosis.mBio · 2026Article
- Incidence of B-cell Malignancies in Patients with Lung Cancer Receiving PD-1 Blockade Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Effects of Astragalus membranaceus injection at Zusanli (ST36) acupoint on lung cancer with COPD.Medical oncology (Northwood, London, England) · 2026Article
- Programmed death-ligand 1 on ex vivo-expanded toll-like-receptor-Bregs prevents allograft rejection by Breg viability promotion, CD4American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Exhausted T cell phenotypes in disseminated coccidioidomycosis.JCI insight · 2026Article
- Nanoplastics impair antitumor NK and CD8⁺ T cell cytotoxicity and antiviral B cell antibody responses to SARS-CoV-2.Scientific reports · 2026Article
- Intratumoral Virus-Like Particles Containing a TLR9 Agonist Combined with Systemic αPD-1 Activate Tumor-Specific CD8+ T Cells.Cancer research communications · 2026Article
- Integrated bioinformatics and in vitro validation reveal the role of CCT5 in immune infiltration and the Wnt pathway in colon cancer.Discover oncology · 2026Article
- Virus-immune signatures reveal distinct clinical phenotypes and predict prognosis in patients with Kaposi's sarcoma.Journal of translational medicine · 2026Article
- Obesity-driven phosphatidylethanolamine dysregulation impairs neuroimmune crosstalk and accelerates Alzheimer's pathogenesis.Molecular neurodegeneration · 2026Article
- Article
- Transcriptional landscape of CD4+ T cells in Systemic Sclerosis.bioRxiv : the preprint server for biology · 2026Article
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Deep Learning-Derived Pathomic Features Predict NCIT Efficacy in Resectable Locally Advanced ESCC: Clinical Utility and Mechanistic Insights.Current oncology (Toronto, Ont.) · 2026Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
In chronic infections and in cancer, persistent antigen stimulation under suboptimal conditions can lead to the induction of T-cell exhaustion. Exhausted T cells are characterized by an increased expression of inhibitory markers and a progressive and hierarchical loss of function. Although cancer-induced exhaustion in CD8 T cells has been well-characterized and identified as a therapeutic target (i.e., via checkpoint inhibition), in-depth analyses of exhaustion in other immune cell types, including CD4 T cells, is wanting. While perhaps attributable to the contextual discovery of exhaustion amidst chronic viral infection, the lack of thorough inquiry into CD4 T-cell exhaustion is particularly surprising given their important role in orchestrating immune responses through T-helper and direct cytotoxic functions. Current work suggests that CD4 T-cell exhaustion may indeed be prevalent, and as CD4 T cells have been implicated in various disease pathologies, such exhaustion is likely to be clinically relevant. Defining phenotypic exhaustion in the various CD4 T-cell subsets and how it influences immune responses and disease severity will be crucial to understanding collective immune dysfunction in a variety of pathologies. In this review, we will discuss mechanistic and clinical evidence for CD4 T-cell exhaustion in cancer. Further insight into the derivation and manifestation of exhaustive processes in CD4 T cells could reveal novel therapeutic targets to abrogate CD4 T-cell exhaustion in cancer and induce a robust antitumor immune response.
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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.