Abstract Purpose: Inflammatory breast cancer (IBC) is a rare yet exceptionally aggressive subtype that accounts for a disproportionate number of breast cancer deaths. A significant barrier to effective treatment is its ability to invade the lymphatic system and evade immune suppression. Emerging research highlights the potential role of C-C chemokine receptor type 7 (CCR7) in driving tumor progression and modulating immune responses within IBC. Baseline changes in CCR7 gene expression have not been reported in IBC. We investigated CCR7 gene amplification, as well as protein expression and spatial distribution in patient tumors, patient-derived xenografts (PDXs), and IBC cell lines. Methods: PDX characterization of non-IBC models for CCR7 was performed using data from the BCM PDX portal (PDX Insights), and sections from selected PDX were stained for multiplex immunofluorescence (mIF) and imaged with a Nikon Ni-E microscope. Cell lines were subjected to immunoblotting for CCR7, and conditioned media were analyzed by ELISA for CCR7 ligands CCL19 and CCL21. Clinical analysis was performed retrospectively, based on an IRB-approved protocol using genomic data from 18 hormone receptor-positive (HR+) HER2-negative (HER2-) IBC and 24 HR-negative (HR-) HER2- IBC cases which were compared to 150 and 104 subtype-matched non-IBC cases, respectively. Results: CCR7 gene expression did not differ between IBC and non-IBC cases independent of subtype. Four IBC patients in each subtype had gain or amplification of CCR7, while six patients in each subtype had deletion. mRNA expression did not correlate with copy number alterations (CNAs). In triple-negative and HER2+ IBC cell lines, CCR7 protein expression was high. CCR7 ligands were not detected in conditioned media of IBC cell lines. Among non-IBC PDX models characterized from PDX Insights, 9/53 demonstrated gain or amplification of CCR7, while 25/53 demonstrated loss. CCR7 gene expression was not concordant with CNAs; we observed 11% CCR7 gene expression in HR+ HER2- IBC patients and 16% in HR- HER2- IBC patients. mIF analysis of PDX sections from BCM-3104, BCM-3807, and BCM-15029, representing CCR7 amplified/high expression (+/+), non-amplified/high expression (-/+), and non-amplified/low expression (-/-), respectively, revealed significant membranous expression only in the +/+ PDX context with concurrent high expression of podoplanin and ligand CCL21. CCR7 protein and gene expression were roughly correlated, with -/+ expression level being intermediate between -/- and +/+. H 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-01-10.
Shivhare et al. (2026) studied this question.