Work

Digital spatial profiling of α-PD-1 treated breast cancer bone metastases reveals region-specific signaling and enrichment of immune-suppressive markers

Year: 2026

Type: article

Abstract: • Digital spatial profiling (DSP) can provide region-specific differences in immune and proliferative pathways in pre-clinical α-PD-1 treated breast cancer bone metastasis samples. • Immune-suppressive markers are enriched in CD45 + cells residing in the endosteum in breast cancer bone metastases. • Proliferation and cell death pathways are preferentially enriched in tumor cells residing in the marrow vs the endosteum. • DSP analysis of breast cancer bone metastases suggests both the endosteum and marrow are pro-tumorigenic, but through distinct enrichment of proliferation and/or immune pathways. Bone is the most common and preferential site for breast cancer metastasis. Upon dissemination to the bone, breast cancer cells engraft into multiple niches, but it is unclear whether there are region-specific differences that may drive breast cancer progression in bone. We used a proteomic digital spatial profiling (DSP) approach to investigate which proliferation, cell death, and immune-related markers and pathways are enriched in immune and cancer cells residing 1) in the bone marrow or 2) along the endosteal surface, in an E0771, α-PD-1 treated pre-clinical model of breast cancer bone metastasis. We selected morphological markers to identify breast cancer cells and immune cells and applied a multiplexed set of probes targeting >70 proteins to characterize breast cancer and immune cell signaling in the marrow and endosteal regions using a digital spatial profiling (DSP) platform. We found multiple immune suppressive markers were enriched in the endosteum, including Foxp3, CD163, CD27, Pd-1, and Pd-l1, while proliferation markers were enriched in tumor cells in the marrow, including p38 Mapk, pan-Ras, Mek1, and phospho-Erk1/2. These findings shed light on the niche-specific proteins and pathways that are activated in breast cancer bone metastases and establish a user-friendly highly multiplexed approach for spatial proteomics in pre-clinical models of bone metastasis.

Source: Journal of bone oncology

DOI: 10.1016/j.jbo.2026.100741

Authors: Déja M. Grant, Gwenyth J. Joseph, Madeline Searcy, Rachelle W. Johnson

Institutions: Meharry Medical College, Vanderbilt University, Vanderbilt University Medical Center

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,990