Related Experiment Video

Updated: Jan 9, 2026

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
07:55

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer

Published on: January 17, 2025

1.7K

Nectin-4 reduces T cell effector function and is a therapeutic target in pancreatic cancer

Max Heiduk1,2,3,4,5, Carolin Beer1, Sarah Cronjaeger1,2,3,4,5

  • 1Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

JCI Insight
|December 9, 2025
PubMed

Insights

Pancreatic cancer (PDAC) shows poor outcomes. Targeting Nectin-4, a protein on tumor cells, with enfortumab vedotin effectively reduced tumor growth in patient-derived models, suggesting a new therapeutic strategy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) presents a significant clinical challenge with limited treatment options and poor patient prognosis.
  • The TIGIT immune checkpoint axis plays a role in tumor immunology, but its specific involvement in PDAC remains incompletely understood.

Purpose of the Study:

  • To investigate the expression and function of TIGIT axis ligands and receptors in PDAC.
  • To evaluate Nectin-4 as a potential therapeutic target in PDAC, including its role in immune evasion and response to targeted therapy.

Main Methods:

  • Analysis of TIGIT axis components via multicolor flow cytometry, immunohistochemistry, and single-cell RNA sequencing in PDAC patient samples (tumor and blood).
  • In vitro assessment of Nectin-4's impact on T cell function.
  • Treatment of patient-derived PDAC organoids with standard chemotherapies and the Nectin-4 targeting antibody-drug conjugate, enfortumab vedotin.

Main Results:

  • Increased TIGIT expression was observed on tumor-infiltrating T cells compared to blood T cells.
  • Nectin-4 expression in tumors correlated with poor patient outcomes and reduced immune cell infiltration.
  • Nectin-4 was found to inhibit T cell effector functions in vitro.
  • Enfortumab vedotin demonstrated significant inhibition of tumor growth in patient-derived PDAC organoids.

Conclusions:

  • Nectin-4 is identified as a novel therapeutic target in PDAC, contributing to immune suppression within the tumor microenvironment.
  • Targeting Nectin-4 with enfortumab vedotin shows promise for PDAC treatment, warranting clinical investigation.
Keywords:
CancerGastroenterologyOncologyT cells

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.4K
Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

10.3K

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.7K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.6K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.7K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.4K
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
3.8K