CCR7 Expression and Spatial Distribution in Inflammatory Breast Cancer: Therapeutic Targeting...

Purpose: Inflammatory breast cancer (IBC) is a rare, highly aggressive subtype marked by rapid proliferation, extensive angio-/lymphangiogenesis, and early metastasis. CCR7, a chemokine receptor involved in immune trafficking, promotes tumor migration toward lymphatics via CCL19/CCL21. This study provides an integrated genomic, protein, spatial, and functional evaluation of CCR7 in IBC to assess its therapeutic potential. Methods: Clinical analysis used genomic data from HR+ HER2- and TNBC IBC compared with subtype-matched non-IBC. CCR7 expression was assessed in IBC and non-IBC cell lines by immunoblotting; ligand secretion (CCL19/CCL21) in tumor and stromal cells was measured by ELISA. CCR7 localization was evaluated using subcellular fractionation and IF, along with testing of a CCR7-blocking antibody. Multiplex IF was performed on BCM PDX models representing distinct CCR7 genomic and protein states. Functional studies included the CCR7 antagonist Navarixin, CCL19/21-induced migration assays, and generation of CCR7 CRISPR knockout clones. Results: CCR7 CNAs occurred in both IBC and non-IBC but did not correlate with mRNA or protein levels. CCR7 protein was broadly expressed, with strongest membranous expression in A3250 and variable levels in IBC-3, SUM-190, and SUM-149. The blocking antibody reduced membranous CCR7 only in A3250, indicating subtype-specific accessibility. IBC cell lines did not secrete CCL19/CCL21, supporting reliance on stromal ligands, which varied by coculture. Across six BCM PDXs, CCR7 was consistently expressed, whereas ligand levels were heterogeneous; MBI-117 showed high CCL19/CCL21. Spatial profiling revealed CCR7+ tumor cells aligned along Podoplanin+ lymphatics with CCL21+ stromal cells and CD163+ macrophages enriched around CCR7+ emboli. Navarixin reduced proliferation in IBC3 and SUM-190 by 96h, and CCL19/21 enhanced migration in A3250 and SUM-149. CCR7-KO SUM-149 clones were generated, with functional analyses ongoing. Conclusion: CCR7 expression in IBC is independent of copy number and supported by a ligand-rich microenvironment that positions CCR7+ tumor cells along lymphatics. Integrated genomic, spatial, and functional data support CCR7 as a therapeutic target in IBC, with studies ongoing. Citation Format: Surbhi Shivhare, Caren Sanchez, Richard Larson, Lacey Dobrolecki, Michael Lewis, Jennifer Chen, Susanne Lin, Anastasiya Evdokimova, Daria Goncharova, Angela Alexander, Azadeh Nasrazadani, Rachel Layman, Bora Lim, Vicente Valero, Anthony Lucci, The MDACC Inflammatory Breast Cancer Team, Wendy A. Woodward. CCR7 expression and spatial distribution in inflammatory breast cancer: A baseline characterization for therapeutic targeting [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 3763.