ArticleNature2015
CEACAM1 regulates TIM-3-mediated tolerance and exhaustion.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 435 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
435 citing papers in PubMed, 2 syntheses or guidelines pooled it, 704 citations in OpenAlex.
- Bibliometric analysis of knowledge maps and future trends of TIM-3 in cancer.Frontiers in oncology · 2026Pooled it
- Single-cell meta-analyses reveal responses of tumor-reactive CXCL13Nature cancer · 2022Pooled it
- Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.British journal of cancer · 2024Trial
- Inhibitory receptor profiles for joint prediction of benefit and toxicity in immune checkpoint blockade.iScience · 2026Review
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- ATP6V0D2 Promotes Atherosclerosis-Associated Vascular Smooth Muscle Cell Dysfunction by Modulating Ferroptosis-Related Signaling.The journal of gene medicine · 2026Article
- TIM3-targeted delivery of venetoclax overcomes drug resistance and reinvigorates NK cell activity in acute myeloid leukemia.Nature cancer · 2026Article
- Molecular Architecture and Clinical Landscape of Immune Checkpoint Receptors and Ligands.Antibodies (Basel, Switzerland) · 2026Review
- Gastric cancer tertiary lymphoid structures in the muscularis propria are associated with therapy resistance and promote immunosuppression.Nature communications · 2026Article
- Serine protease inhibitor from Trichinella spiralis ameliorates diet-induced obesity and adipose tissue inflammation through TIM-3-dependent macrophage reprogramming.PLoS pathogens · 2026Article
- Targeting Immune Checkpoint Proteins in Cancer Therapy and the Potential of RNAi-Based Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Tumor-Associated Platelets Suppress T-cell Function and Promote Immune Evasion in TNBC via the P-selectin/P-selectin Glycoprotein Ligand 1 Pathway.Cancer research communications · 2026Article
- CEACAM1 expression by immunohistochemistry in B-cell lymphomas and plasma cell myeloma.American journal of clinical pathology · 2026Article
- Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Prognostic Impact and Clinicopathological Significance of TIM-3 and LAG-3 Expressions in Laryngeal Squamous Cell Carcinoma.Laryngoscope investigative otolaryngology · 2026Article
- TIM-3 in AML: a janus-faced orchestrator of immune exhaustion and leukemic self-renewal.Cancer cell international · 2026Review
- TIM-3, a potential target for sepsis therapy.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Review
- Mechanism of AGEs-RAGE axis inhibition of ferroptosis in type 2 diabetic colon cancer by regulatory CEACAM1.Scientific reports · 2026Article
- TIM-3 in Cardiovascular Disease.Current heart failure reports · 2026Review
375 more citing papers are in PubMed but not listed here.
Corrections and comments
- Correction · 2016-03-16Doing the Right Thing · Error in Analyses · Error in Image · Error in Results and/or Conclusions · Unreliable Results and/or Conclusions ·
- Erratum issued
- Erratum issued
Authors and funding
24 authors at 11 institutions in 5 countries.
Funding
Abstract
T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers. Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition. Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity.
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.