---
title: "TIGIT-CD155 interaction modulates adapter CAR-T cell function in AML — knockout screen findings"
id: "pubmed-42750591"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42750591"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42750591/"
doi: "10.1080/2162402X.2026.2717853"
published_at: "2026-09-17T09:40:54.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# TIGIT-CD155 interaction modulates adapter CAR-T cell function in AML — knockout screen findings
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42750591
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42750591/)
- **DOI:** [10.1080/2162402X.2026.2717853](https://doi.org/10.1080%2F2162402X.2026.2717853)
- **Published At:** 2026-09-17T09:40:54.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study evaluated immune checkpoint receptors (ICRs) and ligands (ICLs) that may suppress **Adapter CAR (AdCAR)** T-cell activity in acute myeloid leukemia (**AML**), focusing on PD-1, CD96, LAG-3, TIM-3, TIGIT, and CD276. - Multiparametric flow cytometry profiled ICL expression across multiple cancer types, three established AML cell lines, primary AML bone marrow samples, and healthy bone marrow as a reference. - ICL inducibility on AML cells was assessed following **AdCAR-T** cell engagement to understand dynamic ligand upregulation after immune interaction. - CRISPR/Cas9-mediated gene knockouts (KOs) were introduced into AdCAR-T cells targeting PD-1, CD96, CD276, LAG-3, TIM-3, or TIGIT to evaluate functional effects on cytotoxicity in vitro. - PD-1 gene disruption did not significantly increase AdCAR-T-cell cytotoxicity against MOLM-13 wildtype in the authors’ experimental setting. - **TIGIT KO** markedly enhanced AdCAR-T cytotoxicity across five leukemia and lymphoma cell lines in the reported experiments. - Pharmacologic PD-1 blockade produced greater cytotoxicity than PD-1 gene disruption in this model, indicating a difference between systemic blockade and intrinsic receptor loss. - TIGIT blockade produced effects comparable to TIGIT KO, supporting TIGIT as a targetable suppressor of AdCAR-T function. - The authors conclude that **TIGIT KO** is a promising strategy to enhance AdCAR-T efficacy and that immune checkpoint receptor gene disruption could improve therapeutic potency while potentially reducing systemic toxicities associated with immune checkpoint inhibitor therapy. - Specific assay parameters, numerical effect sizes, and detailed experimental conditions were not reported in the provided source abstract.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 17. # Immune checkpoint knockout screen reveals TIGIT-CD155 interaction as a significant modulator of adapter CAR-T cell function in acute myeloid leukemia [Anna-Sophia Mast](https://pubmed.ncbi.nlm.nih.gov/?term=Mast+AS&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Daniel Atar](https://pubmed.ncbi.nlm.nih.gov/?term=Atar+D&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Lara Ruoff](https://pubmed.ncbi.nlm.nih.gov/?term=Ruoff+L&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Sophia Scheuermann](https://pubmed.ncbi.nlm.nih.gov/?term=Scheuermann+S&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-2 "iFIT Cluster of Excellence EXC 2180 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-3 "Hopp-Children's Cancer Center Heidelberg \(KiTZ\), Heidelberg, Germany.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-4 "Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center \(DKFZ\), Germany.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-5 "Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital, Heidelberg, Germany."), [Beate Kristmann](https://pubmed.ncbi.nlm.nih.gov/?term=Kristmann+B&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Peter Lang](https://pubmed.ncbi.nlm.nih.gov/?term=Lang+P&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Christian Martin Seitz](https://pubmed.ncbi.nlm.nih.gov/?term=Seitz+CM&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-3 "Hopp-Children's Cancer Center Heidelberg \(KiTZ\), Heidelberg, Germany.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-4 "Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center \(DKFZ\), Germany.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-5 "Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital, Heidelberg, Germany."), [Patrick Schlegel](https://pubmed.ncbi.nlm.nih.gov/?term=Schlegel+P&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-2 "iFIT Cluster of Excellence EXC 2180 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-6 "Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#full-view-affiliation-7 "Leibniz Institute for Immunotherapy, Regensburg, Germany.") Affiliations Expand ### Affiliations * 1 Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany. * 2 iFIT Cluster of Excellence EXC 2180 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany. * 3 Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany. * 4 Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Germany. * 5 Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital, Heidelberg, Germany. * 6 Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany. * 7 Leibniz Institute for Immunotherapy, Regensburg, Germany. * PMID: **42750591** * DOI: [ 10.1080/2162402X.2026.2717853 ](https://doi.org/10.1080/2162402x.2026.2717853) Item in Clipboard # Immune checkpoint knockout screen reveals TIGIT-CD155 interaction as a significant modulator of adapter CAR-T cell function in acute myeloid leukemia Anna-Sophia Mast et al. Oncoimmunology. 2026. Show details Display options Display options Format Abstract PubMed PMID Oncoimmunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Oncoimmunology%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Oncoimmunology%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42750591/) . 2026 Dec 31;15(1):2717853. doi: 10.1080/2162402X.2026.2717853. Epub 2026 Sep 17. ### Authors [Anna-Sophia Mast](https://pubmed.ncbi.nlm.nih.gov/?term=Mast+AS&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Daniel Atar](https://pubmed.ncbi.nlm.nih.gov/?term=Atar+D&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Lara Ruoff](https://pubmed.ncbi.nlm.nih.gov/?term=Ruoff+L&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Sophia Scheuermann](https://pubmed.ncbi.nlm.nih.gov/?term=Scheuermann+S&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-2 "iFIT Cluster of Excellence EXC 2180 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-3 "Hopp-Children's Cancer Center Heidelberg \(KiTZ\), Heidelberg, Germany.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-4 "Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center \(DKFZ\), Germany.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-5 "Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital, Heidelberg, Germany."), [Beate Kristmann](https://pubmed.ncbi.nlm.nih.gov/?term=Kristmann+B&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Peter Lang](https://pubmed.ncbi.nlm.nih.gov/?term=Lang+P&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany."), [Christian Martin Seitz](https://pubmed.ncbi.nlm.nih.gov/?term=Seitz+CM&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-3 "Hopp-Children's Cancer Center Heidelberg \(KiTZ\), Heidelberg, Germany.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-4 "Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center \(DKFZ\), Germany.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-5 "Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital, Heidelberg, Germany."), [Patrick Schlegel](https://pubmed.ncbi.nlm.nih.gov/?term=Schlegel+P&cauthor_id=42750591)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-1 "Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-2 "iFIT Cluster of Excellence EXC 2180 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-6 "Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42750591/#short-view-affiliation-7 "Leibniz Institute for Immunotherapy, Regensburg, Germany.") ### Affiliations * 1 Department of Hematology, Oncology, Gastroenterology, Nephrology, Rheumatology, University Children's Hospital Tuebingen, Tuebingen, Germany. * 2 iFIT Cluster of Excellence EXC 2180 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany. * 3 Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany. * 4 Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Germany. * 5 Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital, Heidelberg, Germany. * 6 Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany. * 7 Leibniz Institute for Immunotherapy, Regensburg, Germany. * PMID: **42750591** * DOI: [ 10.1080/2162402X.2026.2717853 ](https://doi.org/10.1080/2162402x.2026.2717853) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## 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. **Keywords:** AML; Adapter CAR T cell therapy; immune checkpoint receptor. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## MeSH terms * Cell Line, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%2C+Tumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42750591/) * Gene Knockout Techniques Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gene+Knockout+Techniques%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Gene+Knockout+Techniques) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42750591/) * Hepatitis A Virus Cellular Receptor 2 / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Hepatitis+A+Virus+Cellular+Receptor+2%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nl
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