ArticleOncoimmunology2026
Immune checkpoint knockout screen reveals TIGIT-CD155 interaction as a significant modulator of adapter CAR-T cell function in acute myeloid leukemia.
Article in Oncoimmunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T cell therapy for acute myeloid leukemia (AML) faces critical challenges, including severe on-target off-tumor toxicities, antigen heterogeneity, and primary immune evasion mechanisms. To address these limitations, we previously developed an adapter CAR (AdCAR) platform that enables transient and combinatorial targeting to improve the safety and efficacy of CAR-T-cell therapy in AML. In this study, we further optimized the AdCAR system by investigating the role of immune checkpoint receptors (ICRs), particularly PD-1, CD96, LAG-3, TIM-3, and TIGIT, as well as the immunomodulatory molecule CD276, in suppressing AdCAR-T-cell function. Using multiparametric flow cytometry, we analyzed the expression of immune checkpoint ligands (ICLs) across multiple cancer entities, including three well-characterized AML cell lines, primary AML bone marrow samples, and healthy bone marrow as a reference. We then examined the inducibility of ICLs on AML cells after AdCAR-T-cell engagement. To evaluate the functional impact of immune checkpoint inhibition (ICI), we generated AdCAR-T-cells with CRISPR/Cas9-mediated knockouts (KOs) of PD-1, CD96, CD276, LAG-3, TIM-3, or TIGIT, and analyzed their cytotoxic potential in vitro. In our setting, PD-1 disruption did not significantly enhance AdCAR-T cytotoxicity against MOLM-13 wildtype, while TIGIT KO significantly enhanced AdCAR-T cytotoxicity specifically across five leukemia- and lymphoma-cell lines. Notably, pharmacological PD-1 blockade resulted in greater cytotoxicity than PD-1 gene disruption, whereas TIGIT blockade showed comparable effects to TIGIT KO. Our study identified TIGIT KO as a potent enhancer of AdCAR-T-cell function and supports ICR gene disruption as a promising approach to improve therapeutic efficacy while reducing the systemic toxicities commonly associated with ICI therapy.
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.