ArticleCancer immunology research2013
Increased frequency of ICOS+ CD4 T cells as a pharmacodynamic biomarker for anti-CTLA-4 therapy.
Article in Cancer immunology research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03447678 (Phase II Study to Test Pembrolizumab), which is not on this map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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.
Phase II Study to Test Pembrolizumab (MK-3475) in First Line Treatment of Advanced NSCLC Patients With PD-L1 Low Tumors (<50%)_ PEOPLE TRIAL (Pembrolizumab in Pd-L1 Low Expressors).
Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review.Melanoma research · 2019Pooled it
- Immune biomarkers of response and resistance to ipilimumab and nivolumab in metastatic castration-resistant prostate cancer.Science advances · 2026Trial
- Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma.Nature communications · 2021Trial
- Pre-existing immune status associated with response to combination of sipuleucel-T and ipilimumab in patients with metastatic castration-resistant prostate cancer.Journal for immunotherapy of cancer · 2021Trial
- Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma.Nature medicine · 2020Trial
- Radiotherapy induces responses of lung cancer to CTLA-4 blockade.Nature medicine · 2018Trial
- Ipilimumab plus Lenalidomide after Allogeneic and Autologous Stem Cell Transplantation for Patients with Lymphoid Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Trial
- Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade.Cancer immunology research · 2018Trial
- Immune Activation in Early-Stage Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma.Oncotarget · 2017Trial
- Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Trial
- CD4 T cells require ICOS-mediated PI3K signaling to increase T-Bet expression in the setting of anti-CTLA-4 therapy.Cancer immunology research · 2014Trial
- Clinical and translational results from a phase 1 trial of gemcitabine/nab-paclitaxel with nivolumab/ipilimumab or hydroxychloroquine/ipilimumab in untreated metastatic pancreatic adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- Impaired function of Vγ9Vδ2 T cells in frail elderly.Immunity & ageing : I & A · 2026Article
- ROSE12, a novel anti-CTLA-4 FcγRs binding-enhanced antibody activated by extracellular adenosine triphosphate, shows tumor-selective regulatory T-cell depletion and antitumor efficacy without systemic immune activation.Journal for immunotherapy of cancer · 2026Article
- Inducible T-Cell Co-Stimulator (ICOS) and ICOS Ligand: Dealing With a Two-Faced Cancer Immunoregulatory System.Cancer medicine · 2026Review
- Bhlhe40 Coordinates T Cell Programs with Distinct CD4 and CD8 T Cell Requirements for Anti-PD-1 Versus Anti-CTLA-4.bioRxiv : the preprint server for biology · 2025Article
- Review
- Fc-optimized anti-CTLA-4 antibodies increase tumor-associated high endothelial venules and sensitize refractory tumors to PD-1 blockade.Cell reports. Medicine · 2025Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Pharmacodynamic biomarkers can play an important role in understanding whether a therapeutic agent has "hit its target" to impact biologic function. A pharmacodynamic biomarker for anti-CTLA-4 therapy remains to be elucidated. We previously reported that anti-CTLA-4 therapy increases the frequency of CD4 T cells expressing the inducible costimulator (ICOS) molecule. To determine whether the frequency of ICOS(+) CD4 T cells could be used as a pharmacodynamic biomarker for anti-CTLA-4 therapy, we carried out flow cytometric studies and statistical analyses on data from 56 individuals, which included 10 healthy donors, 36 patients who received anti-CTLA-4 monoclonal antibody (mAb), and 10 patients who received treatment with a different immunomodulatory agent (gp100 DNA vaccine). After treatment with anti-CTLA-4 mAb (ipilimumab; Bristol-Myers Squibb), we detected a statistically significant increase in the frequency of ICOS(+) CD4 T-cells. After two doses of anti-CTLA-4 therapy, the assay was found to have an estimated specificity of 96% [95% confidence interval (CI), 88-100] and sensitivity of 71% (95% CI, 54-85), with positive expression defined as a frequency that is more than the upper bound of 95% CI among baseline samples from all subjects. Our data suggest that an increased frequency of ICOS(+) CD4 T cells measured by flow cytometry can be used as a reproducible pharmacodynamic biomarker to indicate biologic activity in the setting of anti-CTLA-4 therapy, which should enable appropriate immune monitoring to determine whether patients receiving anti-CTLA-4 monotherapy or combination treatment strategies are having an adequate biologic response.
Indexed as
Identifiers
What OpenQuestion holds
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.