Lung Adenocarcinoma Promotion by Chemokine CXCL13 in Transgenic Mouse Models

Chemokine C-X-C motif ligand 13 (CXCL13) is a B lymphocyte chemoattractant that plays an important role in immune system and is involved in the pathogenesis of a number of benign and malignant diseases. Previously, we reported that deficiency in Cxcl13 significantly attenuated air pollutant-induced lung cancer in mice. In this study, we established Cxcl13-overexpressing mouse models to investigate its cancer initiating activity. We found that 15 (51.7%) of 29 mice that received an intratracheal injection of Cxcl13-encoding lentivirus developed lung adenocarcinoma (LUAD), as detected by hematoxylin-eosin (H&E) staining and confirmed by immunohistochemistry for TTF1 in the lung tumor tissues. Of the 21 surfactant protein C (SPC) promoter-driven Cxcl13 transgenic mice, 7 (33.3%) developed LUAD. By single-cell RNA sequencing, we identified a fraction of Ecm1-expressing M2 type macrophages and Itga2+ cancer cells that expressed high level of wnt/β-catenin carcinogenic pathway. Overexpression of CXCL13 in cancer cells promoted CD47 accumulation on the surface of tumor cells to shield themselves from macrophage phagocytosis. Targeting CXCL13 combined with CD47 pathway blockade exerted synergistic anti-tumor efficacy in patient-derived xenograft models of NSCLC. Collectively, our findings indicated that the up-regulation of CXCL13 in lung epithelial cells promotes tumorigenesis, and targeting CXCL13 may provide a potential therapeutic approach for NSCLC. Citation Format: Xiao-Liang Jie, Yang-Tong Liu, Yi-Shuai Tan, San-Hui Gao, Zheng Wang, Gui-Zhen Wang, Guang-Biao Zhou. Lung adenocarcinoma promotion by chemokine CXCL13 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 194.