ArticleCancer immunology research2015
Checkpoint blockade immunotherapy relies on T-bet but not Eomes to induce effector function in tumor-infiltrating CD8+ T cells.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 34 citations in OpenAlex.
- Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort.Annals of hematology · 2021Trial
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Inherited mitochondrial genetics as a predictor of immune checkpoint inhibition efficacy in melanoma.Nature medicine · 2025Article
- Kinase Insert Domain Receptor Q472H Pathogenic Germline Variant Impacts Melanoma Tumor Growth and Patient Treatment Outcomes.Cancers · 2023Article
- Identification of shared characteristics in tumor-infiltrating T cells across 15 cancers.Molecular therapy. Nucleic acids · 2023Article
- The role of mitochondria in the resistance of melanoma to PD-1 inhibitors.Journal of translational medicine · 2023Review
- Targeting breast cancer with a combination of DNT and LAG3 checkpoint blockage and its mechanism.Immunity, inflammation and disease · 2022Article
- Enhancing anti-tumor efficacy and immune memory by combining 3p-GPC-3 siRNA treatment with PD-1 blockade in hepatocellular carcinoma.Oncoimmunology · 2022Article
- Ablation of BATF Alleviates Transplant RejectionFrontiers in immunology · 2022Article
- Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- TargetingFrontiers in immunology · 2021Article
- CD8Journal for immunotherapy of cancer · 2020Article
- Developmental Relationships of Four Exhausted CD8Immunity · 2020Article
- Natural Killer T-Cell Agonist α-Galactosylceramide and PD-1 Blockade Synergize to Reduce Tumor Development in a Preclinical Model of Colon Cancer.Frontiers in immunology · 2020Article
- Indirect Impact of PD-1/PD-L1 Blockade on a Murine Model of NK Cell Exhaustion.Frontiers in immunology · 2020Article
- Checkpoint blockade immunotherapy enhances the frequency and effector function of murine tumor-infiltrating T cells but does not alter TCRβ diversity.Cancer immunology, immunotherapy : CII · 2019Article
- HDAC6 selective inhibition of melanoma patient T-cells augments anti-tumor characteristics.Journal for immunotherapy of cancer · 2019Article
- Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8Frontiers in immunology · 2017Review
- Rescue of Tolerant CD8+ T Cells during Cancer Immunotherapy with IL2:Antibody Complexes.Cancer immunology research · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Coinhibitory receptor blockade is a promising strategy to boost T-cell immunity against a variety of human cancers. However, many patients still do not benefit from this treatment, and responders often experience immune-related toxicities. These issues highlight the need for advanced mechanistic understanding to improve patient outcomes and uncover clinically relevant biomarkers of treatment efficacy. However, the T-cell-intrinsic signaling pathways engaged during checkpoint blockade treatment are not well defined, particularly for combination approaches. Using a murine model to study how effector CD8(+) T-cell responses to tumors may be enhanced in a tolerizing environment, we identified a critical role for the T-box transcription factor T-bet. Combination blockade of CTLA-4, PD-1, and LAG-3 induced T-bet expression in responding tumor/self-reactive CD8(+) T cells. Eradication of established leukemia using this immunotherapy regimen depended on T-bet induction, which was required for IFNγ production and cytotoxicity by tumor-infiltrating T cells, and for efficient trafficking to disseminated tumor sites. These data provide new insight into the success of checkpoint blockade for cancer immunotherapy, revealing T-bet as a key transcriptional regulator of tumor-reactive CD8(+) T-cell effector differentiation under otherwise tolerizing conditions.
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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.