Abstract 6207: Spatial organisation of tumor-infiltrating B cells in Claudin 18.2-expressing advanced gastric cancer predicts response to immune checkpoint inhibition

Abstract Background: Claudin 18.2 (CLDN18.2), a tight junction protein aberrantly expressed during malignant transformation of gastric cancer (GC), has emerged as a key therapeutic target. This study seeks to understand the role of CLDN18.2 in shaping the tumor microenvironment (TME). Methods: This single-center study included 99 patients with advanced gastric cancer treated first-line immune checkpoint inhibition (ICI) agent(s) with chemotherapy. CLDN18.2 expression was determined using immunohistochemistry (VENTANA 43-14A, Roche) on FFPE biopsies, reported as % 2+/3+. To enable a balanced representation of CLDN18.2 status, a median split approach was employed. Samples were also stained with multiplex-IHC (CK, CD4, CD8, FOXP3, CD68 and CD20) to elucidate the corresponding TME. Orthogonal validation was undertaken through independent analyses of whole transcriptome sequencing (WTS) data from 6 cohorts comprising 1,098 GC tumor samples. Cellular neighbourhood (CN) analyses were conducted using a k-nearest neighbors’ algorithm. Survival analyses were conducted with a Cox-proportional hazards model. Results: We retrieved CLDN18.2 status through median-split of CLDN18.2 expression (25.1%), yielding 44 CLDN18.2high samples and 45 CLDN18.2low samples. We observed an increase in CD20+ B cell density in CLDN18.2high samples (p=0.042), whereas no significant differences in cell density were observed in CD4+/CD8+ T cells, CD68+ macrophages and FOXP3+ Tregs. These findings were orthogonally validated utilizing immune cell deconvolution (xCell, Epic Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6207.