ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
CTLA4 blockade broadens the peripheral T-cell receptor repertoire.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 246 papers, 3 of them syntheses that pooled it.
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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
246 citing papers in PubMed, 3 syntheses or guidelines pooled it, 369 citations in OpenAlex.
- Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis.Oncoimmunology · 2020Pooled it
- Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review.Melanoma research · 2019Pooled it
- Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma.Journal for immunotherapy of cancer · 2025Trial
- Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial.Nature medicine · 2023Trial
- Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Tumor-associated antigen-specific T cells with nivolumab are safe and persist in vivo in relapsed/refractory Hodgkin lymphoma.Blood advances · 2022Trial
- Tilsotolimod with Ipilimumab Drives Tumor Responses in Anti-PD-1 Refractory Melanoma.Cancer discovery · 2021Trial
- PD-L1 targeting and subclonal immune escape mediated by PD-L1 mutations in metastatic colorectal cancer.Journal for immunotherapy of cancer · 2021Trial
- Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation.Blood · 2021Trial
- Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer.Nature medicine · 2020Trial
- Trial
- Tremelimumab in Combination With Microwave Ablation in Patients With Refractory Biliary Tract Cancer.Hepatology (Baltimore, Md.) · 2019Trial
- T cell receptor repertoire features associated with survival in immunotherapy-treated pancreatic ductal adenocarcinoma.JCI insight · 2018Trial
- Anti-CMV IgG titer determines organ-specific protection toward immune checkpoint blockade-induced toxicities.Journal for immunotherapy of cancer · 2026Article
- Immune-Mediated Colitis Induced by Immune Checkpoint Inhibitors: Pathophysiology, Clinical Management, and the Emerging Role of Fecal Microbiota Transplantation.Biomedicines · 2026Review
- T cell-intrinsic VISTA expression promotes resistance to CTLA-4 blockade by restricting CD8+ T cell responses.The Journal of clinical investigation · 2026Article
- Liver Transplantation Following Immune Checkpoint Inhibitor Therapy: What Do We Need to Know from Clinical and Immunological Perspective?International journal of molecular sciences · 2026Review
- TCR sequencing in cancer immunology and immunotherapy: what, when, where, why, and how.Journal for immunotherapy of cancer · 2026Review
- Case Report: Durable remission in stage IV melanoma following strategic immune checkpoint inhibitor class rotation and rechallenge.Frontiers in oncology · 2026Article
186 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo evaluate the immunomodulatory effects of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) blockade with tremelimumab in peripheral blood mononuclear cells (PBMC). EXPERIMENTAL
designWe used next-generation sequencing to study the complementarity-determining region 3 (CDR3) from the rearranged T-cell receptor (TCR) variable beta (V-beta) in PBMCs of 21 patients, at baseline and 30 to 60 days after receiving tremelimumab.
resultsAfter receiving tremelimumab, there was a median of 30% increase in unique productive sequences of TCR V-beta CDR3 in 19 out of 21 patients, and a median decrease of 30% in only 2 out of 21 patients. These changes were significant for richness (P = 0.01) and for Shannon index diversity (P = 0.04). In comparison, serially collected PBMCs from four healthy donors did not show a significant change in TCR V-beta CDR3 diversity over 1 year. There was a significant difference in the total unique productive TCR V-beta CDR3 sequences between patients experiencing toxicity with tremelimumab compared with patients without toxicity (P = 0.05). No relevant differences were noted between clinical responders and nonresponders.
conclusionsCTLA4 blockade with tremelimumab diversifies the peripheral T-cell pool, representing a pharmacodynamic effect of how this class of antibodies modulates the human immune system.
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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.