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Thomas Flaig, MD


ASCOBT 2023: Nectin-4 Expression and the Tumor Microenvironment in Bladder Cancer

By: Jenna Carter, PhD
Posted: Thursday, August 17, 2023

The transmembrane protein Nectin cell adhesion molecule 4 (Nectin-4) is highly expressed in urothelial carcinoma. Although use of the antibody-drug conjugate enfortumab vedotin-ejfv, which targets Nectin-4, has been found to induce immunogenic cell death, the correlation between Nectin-4 expression and the tumor microenvironment remains unclear. A study presented at the 2023 American Society of Clinical Oncology (ASCO) Breakthrough meeting (Abstract 74) in Yokohama, Japan, by Akihide Yoshimi, MD, PHD , of the Cancer RNA Research Unit, National Cancer Center Research Institute, Tokyo, and colleagues found that Nectin-4 mRNA expression was positively correlated with tumor grade, lymph vascular invasion, and tumor mutation burden.

A total of 389 patients with bladder cancer were included in this study, 44 of whom were diagnosed with a variant histology. The investigators used a comprehensive data set to examine whole-exome and RNA-sequencing, immunohistochemistry, and clinicopathologic records. Eligible patients (n = 378) were also classified into three groups according to H-score: the low group (H-score = 0; n = 93), the medium group (H-score = 10–190; n = 202), and the high group (H-score = 200–300; n = 83).

The investigators reported that overall survival was significantly worse in the low H-score group compared with the medium and high H-score groups (P < .0001). Additional findings revealed gene set enrichment identified that epithelial-mesenchymal transition–related programs and immune-related cytokines were activated in the low H-score group. A total of 73 immune checkpoint comparisons were conducted. These evaluations revealed that putative immune checkpoint gene expression significantly differed between the low and high H-score groups. Based on these findings, study authors concluded that differential immune therapy strategies that consider Nectin-4 expression levels may prove to be beneficial for patients with bladder cancer.

Disclosure: Dr. Yoshimi has served as a consultant or advisor to Nihonkayaku and has received research funding from Chugai Pharma. The other study authors reported no conflicts of interest.

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