ArticleJournal of translational medicine2026
TIPE2 knockdown enhances the anti-tumor efficacy of NKG2D CAR-T cells against pancreatic cancer via activating NF-κb signaling pathway.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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
3 citing papers in PubMed.
- Impact of Glycine-Serine Linker on Target Antigen Binding and Subsequent CD37CAR-T Performance.International journal of molecular sciences · 2026Article
- Review
- Tumor-associated macrophages and lineage plasticity in prostate cancer: from established myeloid programs to emerging spatial hypotheses.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is an intracellular immune checkpoint protein known to suppress T cell activation and effector function. Despite its role in limiting T cell responses, CAR-T cells are prone to TIPE2-mediated inhibitory signaling. We therefore hypothesized that inhibiting this immune checkpoint would enhance CAR-T cell anti-tumor function.
methodsTo overcome TIPE2-mediated negative regulation, we engineered a novel second-generation NKG2D-based CAR-T cell by incorporating TIPE2-targeting shRNA sequences directly into the CAR construct. TIPE2 knockdown efficiency in the CAR constructs was measured by qPCR and western blot analysis. The functional and mechanistic properties of TIPE2-downregulated CAR-T cells were evaluated in vitro by flow cytometry, including analysis of activation, cytotoxicity, exhaustion, apoptosis, proliferation, and differentiation. Antitumor efficacy was further validated in vivo using a preclinical pancreatic cancer mouse model.
resultsFlow cytometry analysis revealed that TIPE2-deficient CAR-T cells exhibited significantly higher expression of activation (CD69), degranulation (CD107a), cytotoxic (GzmB), and cytokine (IFN-γ) markers, resulting in more efficient tumor cell elimination compared to conventional CAR-T cells. TIPE2 silencing also reduced T cell exhaustion, lowered susceptibility to apoptosis, and enhanced proliferation when co-cultured with Panc-28 pancreatic cancer cells. Moreover, TIPE2 inhibition skewed CAR-T cells differentiation towards an effector phenotype (T
conclusionWe successfully developed TIPE2-downregulated NKG2D-CAR-T cells that exhibited enhanced activation and cytotoxicity while limiting apoptosis and exhaustion against NKG2D ligand-expressing pancreatic tumors, highlighting TIPE2 as a promising intracellular immune checkpoint target for optimizing CAR-T cell therapy in solid tumors.
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.