ArticleThe Journal of experimental medicine2015
Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04426669 (A Phase I/II Trial in Patients With Metastatic Gastrointestinal Epithelial Cancer Administering Tumor-Infiltrating Lymphocytes in Which the Gene Encoding CISH Was Inactivated Using the CRISPR/Cas9 System), which is not on this map. Cited by 123 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.
A Phase I/II Trial in Patients With Metastatic Gastrointestinal Epithelial Cancer Administering Tumor-Infiltrating Lymphocytes in Which the Gene Encoding CISH Was Inactivated Using the CRISPR/Cas9 System
Who cites it
123 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype.Scientific reports · 2020Trial
- Post-COVID impairment of T cell responses to community-acquired pathogens can be modified by activating cellular metabolism.PLoS pathogens · 2026Article
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- Non-viral targeted integration at the CISH locus enables CAR-NK cell engineering with enhanced anti-tumor activity.Molecular therapy. Oncology · 2026Article
- Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Preventing trogocytosis by cathepsin B inhibition augments CAR T-cell function.Signal transduction and targeted therapy · 2026Article
- Article
- Using cell-specific late-phase asthma mRNA biomarkers to repurpose drugs that concurrently reverse disease signatures across multiple immune cell-types.PLoS computational biology · 2026Article
- Targeting organelle function in T cells for cancer immunotherapy.Nature reviews. Immunology · 2026Review
- Non-clinical safety considerations on genome editing using the CRISPR/Cas system.Genes & diseases · 2026Review
- Conditional T and NK cell antagonism by a giant and highly conserved orthopoxvirus virulence factor.Research square · 2026Article
- New insight into the role of SOCS family in immune regulation and autoimmune pathogenesis.Journal of advanced research · 2026Review
- CISH, a key intracellular checkpoint, in comparison and combination to existing and emerging cancer immune checkpoints.Communications biology · 2026Article
- Post-COVID impairment of memory T cell responses to community-acquired pathogens can be rectified by activating cellular metabolism.bioRxiv : the preprint server for biology · 2026Article
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- Cytokine inducible SH2-containing protein: a versatile negative regulator of cytokine receptor signaling.Frontiers in immunology · 2026Review
- The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.Journal for immunotherapy of cancer · 2025Review
- Preventing trogocytosis by cathepsin B inhibition augments CAR T cell function.bioRxiv : the preprint server for biology · 2025Article
- CRISPR/Cas technologies in pancreatic cancer research and therapeutics: recent advances and future outlook.Discover oncology · 2025Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Improving the functional avidity of effector T cells is critical in overcoming inhibitory factors within the tumor microenvironment and eliciting tumor regression. We have found that Cish, a member of the suppressor of cytokine signaling (SOCS) family, is induced by TCR stimulation in CD8(+) T cells and inhibits their functional avidity against tumors. Genetic deletion of Cish in CD8(+) T cells enhances their expansion, functional avidity, and cytokine polyfunctionality, resulting in pronounced and durable regression of established tumors. Although Cish is commonly thought to block STAT5 activation, we found that the primary molecular basis of Cish suppression is through inhibition of TCR signaling. Cish physically interacts with the TCR intermediate PLC-γ1, targeting it for proteasomal degradation after TCR stimulation. These findings establish a novel targetable interaction that regulates the functional avidity of tumor-specific CD8(+) T cells and can be manipulated to improve adoptive cancer immunotherapy.
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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.