Trial reportCancer immunology research2014
CD4 T cells require ICOS-mediated PI3K signaling to increase T-Bet expression in the setting of anti-CTLA-4 therapy.
Trial report in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The trial behind it
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade.Cancer immunology research · 2018Trial
- Development and evaluation of the first-in-class nanobody based PET tracer targeting human inducible T-cell co-stimulator receptor.EJNMMI research · 2026Article
- IRES-based RNAs expressing co-stimulatory molecules: Promising candidates for cancer immunotherapy.Molecular therapy. Nucleic acids · 2026Article
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Macrophage-Dendritic Cell-T-Cell Tetrads Orchestrate Antitumor Immunity and Response to Checkpoint Blockade.bioRxiv : the preprint server for biology · 2025Article
- TIGIT/SHIP-1/RelB regulating Th1 inflammation in smoking induced COPD.Respiratory research · 2025Article
- PD-1 expressing islet-specific CD4Immunology and cell biology · 2025Article
- Fc-optimized anti-CTLA-4 antibodies increase tumor-associated high endothelial venules and sensitize refractory tumors to PD-1 blockade.Cell reports. Medicine · 2025Article
- Advances in cancer immunotherapy: historical perspectives, current developments, and future directions.Molecular cancer · 2025Review
- Neoadjuvant immune checkpoint therapy: Enabling insights into fundamental human immunology and clinical benefit.Cancer cell · 2025Review
- Unraveling Th subsets: insights into their role in immune checkpoint inhibitor therapy.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis.Journal for immunotherapy of cancer · 2025Article
- Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse model.Journal of translational medicine · 2025Article
- Interruption of the intratumor CD8Cancer cell · 2024Article
- ICOS costimulation in combination with CTLA-4 blockade remodels tumor-associated macrophages toward an antitumor phenotype.The Journal of experimental medicine · 2024Article
- Current Technologies and Future Perspectives in Immunotherapy towards a Clinical Oncology Approach.Biomedicines · 2024Review
- ICOS DNA methylation regulates melanoma cell-intrinsic ICOS expression, is associated with melanoma differentiation, prognosis, and predicts response to immune checkpoint blockade.Biomarker research · 2023Article
- Inducible Costimulator-C-X-C Motif Chemokine Receptor 3 Signaling is Involved in Chronic Obstructive Pulmonary Disease Pathogenesis.International journal of chronic obstructive pulmonary disease · 2022Article
- B3GNT3: A prognostic biomarker associated with immune cell infiltration in pancreatic adenocarcinoma.Oncology letters · 2021Article
- Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.Pharmaceutics · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The transcription factor T-bet controls the Th1 genetic program in T cells for effective antitumor responses. Anti-CTLA-4 immunotherapy elicits dramatic antitumor responses in mice and in human patients; however, factors that regulate T-bet expression during an antitumor response mediated by anti-CTLA-4 remain to be elucidated. We were the first to report that treatment with anti-CTLA-4 led to an increase in the frequency of T cells expressing inducible costimulator (ICOS). In both treated patients and mice, our data revealed that CD4(+)ICOS(hi) T cells can act as effector T cells, which produce the Th1 cytokine IFN-γ. We also showed in a small retrospective analysis that an increased frequency of CD4(+)ICOS(hi) T cells correlated with better clinical outcome and the absence of ICOS or its ligand (ICOSL) in mouse models led to impaired tumor rejection. Here, we show that CD4(+)ICOS(hi) T cells from anti-CTLA-4-treated patients had an increase in signaling via the phospoinositide-3-kinase (PI3K) pathway and an increase in expression of T-bet. An ICOS-specific siRNA transfected into human T cells led to diminished PI3K signaling and T-bet expression. Therefore, we hypothesized that ICOS, and specifically ICOS-mediated PI3K signaling, was required for T-bet expression. We conducted studies in ICOS-deficient and ICOS-YF mice, which have a single amino acid change that abrogates PI3K signaling by ICOS. We found that ICOS-mediated PI3K signaling is required for T-bet expression during an antitumor response elicited by anti-CTLA-4 therapy. Our data provide new insight into the regulation of T-bet expression and suggest that ICOS can be targeted to improve Th1 antitumor responses.
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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.